Applicators for applying transcutaneous analyte sensors and associated methods of manufacture

ABSTRACT

Applicators for applying an on-skin assembly to skin of a host and methods of their use and/or manufacture are provided. An applicator includes an insertion assembly configured to insert at least a portion of the on-skin assembly into the skin of the host, a housing configured to house the insertion assembly, the housing comprising an aperture through which the on-skin assembly can pass, an actuation member configured to, upon activation, cause the insertion assembly to insert at least the portion of the on-skin assembly into the skin of the host, and a sealing element configured to provide a sterile barrier and a vapor barrier between an internal environment of the housing and an external environment of the housing.

INCORPORATION BY REFERENCE TO RELATED APPLICATIONS

Any and all priority claims identified in the Application Data Sheet, orany correction thereto, are hereby incorporated by reference under 37CFR 1.57. This application is a continuation of U.S. application Ser.No. 16/011,527, filed Jun. 18, 2018, which claims the benefit of U.S.Provisional Application No. 62/521,969 filed Jun. 19, 2017. Theaforementioned application is incorporated by reference herein in itsentirety, and is hereby expressly made a part of this specification.

FIELD

An applicator for applying an on-skin assembly to skin of a host andmethods of their use and/or manufacture are provided. More particularly,apparatuses for applying a transcutaneous analyte assembly to skin of ahost for accurately measuring blood glucose of the host and methods oftheir use and/or manufacture are provided.

BACKGROUND

Diabetes mellitus is a disorder in which the pancreas cannot createsufficient insulin (Type I or insulin dependent) and/or in which insulinis not effective (Type 2 or non-insulin dependent). In the diabeticstate, the victim suffers from high blood sugar, which can cause anarray of physiological derangements associated with the deterioration ofsmall blood vessels, for example, kidney failure, skin ulcers, orbleeding into the vitreous of the eye. A hypoglycemic reaction (lowblood sugar) can be induced by an inadvertent overdose of insulin, orafter a normal dose of insulin or glucose-lowering agent accompanied byextraordinary exercise or insufficient food intake.

Conventionally, a person with diabetes carries a self-monitoring bloodglucose (SMBG) monitor, which typically requires uncomfortable fingerpricking methods. Due to the lack of comfort and convenience, a personwith diabetes normally only measures his or her glucose levels two tofour times per day. Unfortunately, such time intervals are spread so farapart that the person with diabetes likely finds out too late of ahyperglycemic or hypoglycemic condition, sometimes incurring dangerousside effects. Glucose levels may be alternatively monitored continuouslyby a sensor system including an on-skin sensor assembly. The sensorsystem may have a wireless transmitter which transmits measurement datato a receiver which can process and display information based on themeasurements.

This Background is provided to introduce a brief context for the Summaryand Detailed Description that follow. This Background is not intended tobe an aid in determining the scope of the claimed subject matter nor beviewed as limiting the claimed subject matter to implementations thatsolve any or all of the disadvantages or difficulties presented above.

SUMMARY

The present apparatuses and methods of manufacture relate to systems andmethods for measuring an analyte in a host, systems and methods formanufacturing a transcutaneous analyte measurement system, and systemsand methods for applying a transcutaneous analyte measurement system toskin of a host. The various embodiments of the present systems andmethods have several features, no single one of which is solelyresponsible for their desirable attributes. Without limiting the scopeof the present embodiments as expressed by the claims that follow, theirmore prominent features now will be discussed briefly. After consideringthis discussion, and particularly after reading the section entitled“Detailed Description,” one will understand how the features of thepresent embodiments provide the advantages described herein.

According to a first aspect, an applicator for applying an on-skinassembly to skin of a host is provided. The applicator includes aninsertion assembly configured to insert at least a portion of the sensorassembly into the skin of the host. The applicator includes a housingconfigured to house the insertion assembly. The housing includes anaperture through which the sensor assembly is configured to pass. Theapplicator includes an actuation member configured to, upon activation,cause the insertion assembly to insert at least the portion of thesensor assembly into the skin of the host. The applicator includes asealing element configured to provide a sterile barrier and a vaporbarrier between an internal environment of the housing and an externalenvironment of the housing.

In some embodiments, the sealing element is releasable from theapplicator. In some embodiments, the applicator further includes theon-skin assembly. In some embodiments, the on-skin assembly comprises asensor. In some embodiments, the on-skin assembly comprises atransmitter. In some embodiments the on-skin assembly comprises anadhesive layer configured to adhere the on-skin assembly to the skin ofthe host. In some embodiments, the applicator further includes a supportmember configured to inhibit at least lateral movement of the insertionassembly. In some embodiments, the support member comprises anelastomeric membrane. In some embodiments, the insertion assemblycomprises a needle. In some embodiments, the applicator further includesone or more ridges or recesses configured to provide a tactileindication of grip for the host. In some embodiments, the applicator hasa cross-sectional shape configured to provide a tactile indication ofgrip for the host. In some embodiments, the applicator further includesat least one protrusion configured to inhibit rolling of the applicator.In some embodiments, the housing comprises a vent configured to bepermeable to a sterilizing gas. In some embodiments, the sealing elementis configured to seal the vent. In some embodiments, the sealing elementis configured to seal both the aperture and the actuation member. Insome embodiments, the actuation member comprises a material that ispermeable to a sterilizing gas. In some embodiments, the sealing elementcomprises at least one of a metallic foil (e.g. aluminum, titanium), ametallic substrate, aluminum oxide coated polymer, parylene, a polymercoated with a metal applied via vapor metallization, silicon dioxidecoated polymer, or any material having a moisture vapor transmissionrate less than 10 grams/100 in{circumflex over ( )}2 or preferably lessthan 1 grams/100 in{circumflex over ( )}2.

In some embodiments, the sealing element comprises a removable capconfigured to couple with a portion of the housing. In some embodiments,the removable cap is configured to couple with a proximal portion of thehousing. In some embodiments, the removable cap is configured to couplewith a distal portion of the housing. In some embodiments, the removablecap is configured to couple with the housing in a single axialorientation. In some embodiments, the removable cap is configured tocouple with the portion of the housing via threads. In some embodiments,the removable cap is configured to couple with the portion of thehousing via a frangible member. In some embodiments, the frangiblemember is configured to provide a tamper indication when broken. In someembodiments, the sealing element further comprises an o-ring configuredto provide a seal between the removable cap and the housing. In someembodiments, the removable cap covers the actuation member.

In some embodiments, the applicator further includes a tamper indicator.In some embodiments, the sealing element comprises a first layer beingpermeable to a sterilizing gas and a second layer being substantiallyimpermeable to water vapor. In some embodiments, the sealing elementcomprises a first layer being substantially impermeable to water vaporand sealing the aperture. In some embodiments, the sealing elementfurther comprises a second layer being substantially impermeable towater vapor and sealing the actuation member. In some embodiments, thesealing element comprises a peelable layer coupled to at least a portionof the housing. In some embodiments, the peelable layer is configured toprovide a tamper indication when removed. In some embodiments, thepeelable layer is configured to seal a distal opening of the housing. Insome embodiments, the peelable layer is configured to further seal theactuation member. In some embodiments, the peelable layer is configuredto seal a vent configured to be permeable to a sterilizing gas. In someembodiments, the vent is disposed on a side of the housing. In someembodiments, a porous polymeric component is inserted into the vent.

In some embodiments, the sealing element comprises a flexible memberdisposed over at least a portion of the housing. In some embodiments,the flexible member comprises an elastomer. In some embodiments, theflexible member covers the actuation member. In some embodiments, theflexible member is operatively coupled to the actuation member. In someembodiments, the flexible member has a bistable configuration so as toprovide a visual indication of deployment after activation. In someembodiments, the sealing element comprises a frangible member. In someembodiments, the frangible member covers the actuation member, andwherein removal of the frangible member exposes the actuation member foractivation.

In some embodiments, the sealing element comprises a cup having aremovable lid. In some embodiments, the cup is configured to becollapsible after removal of the lid. In some embodiments, the cup isconfigured to seal applicator from an environment outside the cup. Insome embodiments, the cup comprises an on-skin assembly alignmentfeature. In some embodiments, the cup comprises a needle protectionfeature. In some embodiments, the sealing element comprises a plugconfigured to couple to the housing via a friction fit.

In some embodiments, the actuation member is disposed on a side of thehousing. In some embodiments, the actuation member is disposed on aproximal portion of the housing. In some embodiments, the actuationmember is recessed into the proximal portion of the housing. In someembodiments, the actuation member comprises a cap coupled to a proximalportion of the housing. In some embodiments, the actuation member isconfigured to be activated by moving the cap in a distal direction. Insome embodiments, the sealing element further comprises a sealing layerdisposed between the cap and the housing. In some embodiments, the capcomprises a protrusion configured to pierce the sealing layer andthereby activate the insertion assembly. In some embodiments, theinsertion assembly is driven by a spring force. In some embodiments, theneedle is retracted from the insertion assembly after the insertionassembly inserts the on-skin assembly. In some embodiments, theapplicator further includes a safety member configured to preventactivation of the actuation member. In some embodiments, the safetymember comprises a frangible member, the frangible member beingconfigured to prevent activation of the actuation member, at least untilthe frangible member is broken.

In some embodiments, the sealing element comprises a first portioncomprising a plurality of perforations and an adhesive layer disposed ona first side of the first portion. In some embodiments, the sealingelement further comprises a second portion disposed adjacent to thefirst side of the first portion, the second portion configurable in afirst configuration wherein the first portion is spatially separatedfrom the second portion and a second configuration wherein the secondportion is adhered to the first portion via the adhesive layer, whereinthe sealing element is permeable to a sterilizing gas in the firstconfiguration, and the sealing element is impermeable to the sterilizinggas in the second configuration. In some embodiments, the second portionis configured to transition from the first configuration to the secondconfiguration when the applicator is subjected to a partial vacuumexceeding a threshold. In some embodiments, the housing is disposable.

In a second aspect, a method of manufacturing an applicator configuredto apply a sensor assembly to skin of a host is provided. The methodincludes providing an insertion assembly configured to insert at least aportion of the sensor assembly into the skin of the host. The methodincludes providing a housing configured to house the insertion assembly.The housing comprising an aperture through which the sensor assembly isconfigured to pass. The method includes providing an actuation memberconfigured to, upon activation, cause the insertion assembly to insertat least the portion of the sensor assembly into the skin of the host.The method includes providing a releasable sealing element configured toprovide a sterile barrier and a vapor barrier between an internalenvironment of the housing and an external environment of the housing.

In a third aspect, a method of manufacturing an applicator configured toapply a sensor assembly to skin of a host is provided. The methodincludes providing an insertion assembly configured to insert at least aportion of the sensor assembly into the skin of the host. The methodincludes providing a housing configured to house the insertion assembly.The housing comprising an aperture through which the sensor assembly isconfigured to pass. The method includes providing an actuation memberconfigured to, upon activation, cause the insertion assembly to insertat least the portion of the sensor assembly into the skin of the host.The method includes exposing at least an internal environment of thehousing to a sterilizing gas. The method includes allowing for egress ofthe sterilizing gas from the internal environment of the housing. Themethod includes sealing the internal environment of the housing from anexternal environment of the housing.

In some embodiments, at least sealing the internal environment of thehousing from an external environment of the housing is performedsimultaneously for a plurality of applicators. In some embodiments,sealing the internal environment of the housing from an externalenvironment of the housing comprises subjecting the plurality ofapplicators to a partial vacuum exceeding a threshold such that asealing element of each of the plurality of applicators transitions frombeing permeable to the sterilizing gas to being impermeable to thesterilizing gas. In some embodiments, sealing the internal environmentof the housing from an external environment of the housing comprisessubjecting the plurality of applicators to a physical force sufficientto cause a sealing element of each of the plurality of applicators totransition from a first physical configuration permeable to thesterilizing gas to a second physical configuration impermeable to thesterilizing gas. In some embodiments, sealing the internal environmentof the housing from an external environment of the housing comprisessubjecting a sealing element, comprising a plurality of perforations, ofeach the plurality of applicators to a temperature sufficient to atleast partially melt each of the sealing elements thereby sealing theplurality of perforations in each of the sealing elements. In someembodiments, sealing the internal environment of the housing from anexternal environment of the housing comprises subjecting a sealingelement, comprising a porous polymeric component, of each of theplurality of applicators to a temperature sufficient to form a sinteredlayer in the porous polymeric component of each sealing element. In someembodiments, sealing the internal environment of the housing from anexternal environment of the housing comprises depositing a layerimpermeable to the sterilizing gas on at least a portion of each of theplurality of applicators. In some embodiments, the layer comprises atleast one of aluminum oxide, parylene, a vapor metallization, silicondioxide, or a material applied via ion beam sputtering.

In some embodiments, an applicator for applying an on-skin assembly toskin of a host is provided. The applicator may include an insertionassembly configured to insert at least a portion of the on-skin assemblyinto the skin of the host. The housing may be configured to receive theinsertion assembly. The housing may comprise an aperture through whichthe on-skin assembly is configured to pass. The applicator may comprisean actuation member configured to, upon activation, actuate theinsertion assembly to insert at least the portion of the on-skinassembly into the skin of the host. The applicator may comprise aremovable cap configured to couple with a portion of the housing. Theapplicator may comprise a layer comprising a gas permeable material, thesealing element configured to allow for ingress and egress of asterilizing gas.

In some embodiments, the removable cap includes an aperture located at abottom end of the removable cap. In some embodiments, the layer iscoupled to the bottom of the removable cap and encloses the aperture.The removable cap may include a raised platform from the bottom end ofthe removable cap. In some embodiments, the raised platform is spaced apredetermined distance from the on-skin assembly. The raised platformmay include a plurality of channels. The plurality of channels may bespaced equidistantly along the circumference of the raised platform. Theplurality of channels may be configured to allow for ingress of thesterilizing gas into the housing and egress of the sterilizing gas outof the housing.

In some embodiments, the applicator includes a safety feature to preventactuation of the actuation member. The safety feature can be unlocked bypressing the housing in a distal direction. The pressing of the housingin a distal direction actuates the housing along an inner housing of theapplicator. The actuation member may be aligned with a trigger arm, theactuation member configured to laterally actuate and deflect the triggerarm. In some embodiments, the removable cap is configured to couple witha proximal portion of the housing. In some embodiments, the removablecap is configured to couple with a distal portion of the housing.

This Summary is provided to introduce a selection of concepts in asimplified form. The concepts are further described in the DetailedDescription section. Elements or steps other than those described inthis Summary are possible, and no element or step is necessarilyrequired. This Summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended foruse as an aid in determining the scope of the claimed subject matter.The claimed subject matter is not limited to implementations that solveany or all disadvantages noted in any part of this disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features, aspects, and advantages are described belowwith reference to the drawings, which are intended to illustrate, butnot to limit, the invention. In the drawings, like reference charactersdenote corresponding features consistently throughout similarembodiments.

FIG. 1A is an exploded cross-sectional view of an applicator forapplying an on-skin assembly to skin of a host including a sealingelement, in accordance with some embodiments.

FIG. 1B is a zoomed cutaway view of the applicator of FIG. 1A, furtherillustrating an insertion assembly and the on-skin assembly, inaccordance with some embodiments.

FIG. 1C illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a sealing element having afrangible member, in accordance with some embodiments.

FIG. 2A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a peelable tamperindicator, in accordance with some embodiments.

FIG. 2B is a partially exploded perspective view of the applicator ofFIG. 2A.

FIG. 3A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including another tamper indicator,in accordance with some embodiments.

FIG. 3B is a zoomed cross-sectional view of the applicator of FIG. 3A,wherein a sealing element comprises an o-ring, in accordance with someembodiments.

FIG. 3C is zoomed cross-sectional view of the applicator of FIGS. 3A and3B, in accordance with some embodiments.

FIG. 4A illustrates a perspective view of another applicator forapplying an on-skin assembly to skin of a host including a tamperindicator, in accordance with some embodiments.

FIG. 4B is a partially exploded view of the applicator of FIG. 4A.

FIG. 5A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a tactile indication ofgrip for the host, in accordance with some embodiments.

FIG. 5B is a partially exploded view of the applicator of FIG. 5A.

FIG. 6A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a sealing elementconfigured to couple with a housing in a single axial orientation, inaccordance with some embodiments.

FIG. 6B is another perspective view of the applicator of FIG. 6A, shownwith the sealing element separated from the housing

FIG. 7A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a frangible memberconfigured to prevent activation of an actuation member, in accordancewith some embodiments.

FIG. 7B is a partially exploded view of the applicator of FIG. 7A.

FIG. 8A illustrates a perspective view of another applicator forapplying an on-skin assembly to skin of a host including a frangiblemember configured to prevent activation of an actuation member, inaccordance with some embodiments.

FIG. 8B is a cross-sectional view of the applicator of FIG. 8A in apre-deployment configuration.

FIG. 8C is a cross-sectional view of the applicator of FIG. 8A in adeployed configuration.

FIG. 9A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including an actuation memberconfigured as a cap disposed over a housing of the applicator, inaccordance with some embodiments.

FIG. 9B is a cross-sectional view of the applicator of FIG. 9A in apre-deployment configuration.

FIG. 9C is a cross-sectional view of the applicator of FIG. 9A in adeployed configuration.

FIG. 10A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a removable cap configuredas a sealing element, in accordance with some embodiments.

FIG. 10B is a partially exploded view of the applicator of FIG. 10A.

FIG. 11A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a flexible member disposedover at least a portion of the applicator housing, in accordance withsome embodiments.

FIG. 11B is a detail view of a portion of the flexible member of FIG.11A disposed over an actuation member.

FIG. 12A illustrates a cross-sectional view of an applicator forapplying an on-skin assembly to skin of a host including a flexiblemember having a bistable configuration that provides a visual indicationof deployment, in accordance with some embodiments.

FIG. 12B is a detail cross-sectional view of a portion of the bistableconfiguration of the flexible member of FIG. 12A.

FIG. 13A is an exploded view of an applicator for applying an on-skinassembly to skin of a host including a frangible member configured tocover an actuation member, in accordance with some embodiments.

FIG. 13B is an assembled view of the applicator of FIG. 13A.

FIG. 13C illustrates a perspective view of the applicator of FIGS. 13Aand 13B having the frangible member removed, thereby exposing anactuation member.

FIG. 14 illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a frangible portion havinga flexible tab molded around an actuation member, in accordance withsome embodiments.

FIG. 15A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a peelable layer configuredto seal a distal opening in a housing and to further seal an actuationmember, in accordance with some embodiments.

FIG. 15B illustrates the applicator of FIG. 15A having the peelablelayer removed.

FIG. 16A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a peelable layer configuredto seal a distal opening in a housing, to further seal an actuationmember, and to further seal vent permeable to a sterilizing gas, inaccordance with some embodiments.

FIG. 16B is a partially exploded view of the applicator of FIG. 16A.

FIG. 17A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a peelable layer configuredto seal a distal opening in a housing and a inset plug configured toseal an actuation member, in accordance with some embodiments.

FIG. 17B illustrates the applicator of FIG. 17A with the inset plugremoved.

FIG. 17C illustrates the applicator of FIG. 17A with the peelable layerat least partially removed.

FIG. 18A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a removable cap configuredto seal an actuation member and a peelable layer configured to seal adistal opening in a housing, in accordance with some embodiments.

FIG. 18B is a partially exploded view of the applicator of FIG. 18A.

FIG. 19A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a frangible cap configuredto seal an actuation member and a peelable layer configured to seal adistal opening in a housing, in accordance with some embodiments.

FIG. 19B is a partially exploded view of the applicator of FIG. 19A.

FIG. 20A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a first peelable layerconfigured to seal a distal opening in a housing and a second peelablelayer configured to seal an actuation member disposed in a proximalopening in the housing, in accordance with some embodiments.

FIG. 20B illustrates the actuation member of the applicator of FIG. 20A.

FIG. 21A illustrates a perspective view of another applicator forapplying an on-skin assembly to skin of a host including a inset plugconfigured to seal an actuation member and a peelable layer configuredto seal a distal opening in a housing, in accordance with someembodiments.

FIG. 21B is a detail view of the applicator of FIG. 21A having thepeelable layer removed.

FIG. 21C is a detail view of the applicator of FIG. 21A having the insetcap removed.

FIG. 22A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a first peelable layerconfigured to seal a distal opening in a housing and to seal a ventpermeable to a sterilizing gas and a second peelable layer configured toseal an actuation member disposed in a proximal opening in the housing,in accordance with some embodiments.

FIG. 22B is a partially exploded view of the applicator of FIG. 22A.

FIG. 23 illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host configured to fit within acollapsible cup having a removable lid, in accordance with someembodiments.

FIG. 24A illustrates a perspective view of a cup having a removable lidand configured to enclose an applicator for applying an on-skin assemblyto skin of a host, in accordance with some embodiments.

FIG. 24B is a cross-sectional view of the cup and applicator of FIG.24A.

FIG. 25A is a cross-sectional view of an applicator for applying anon-skin assembly to skin of a host including an actuation member that ispermeable to a sterilizing gas, in accordance with some embodiments.

FIG. 25B is a detail view of the actuation member of FIG. 25A.

FIG. 26A is a cross-sectional view of a soluble moisture barrier havinga plurality of perforations for an applicator for applying an on-skinassembly to skin of a host, in accordance with some embodiments.

FIG. 26B is a cross-sectional view of the soluble moisture barrier ofFIG. 26A after heating such that the moisture barrier has melted and theplurality of perforations are sealed.

FIG. 27A is a cross-sectional view of a moisture barrier including anelastomeric layer having a portion permeable to a sterilizing gas and aperforated layer configured to pass a permeable gas when the elastomericlayer and the perforated layer are in a first orientation with respectto each other, in accordance with some embodiments.

FIG. 27B is a cross-sectional view of the moisture barrier of FIG. 27Aillustrating the elastomeric layer and the perforated layer in a secondorientation with respect to each other such that the moisture barrier isimpermeable to the sterilizing gas and to moisture, in accordance withsome embodiments.

FIG. 28A illustrates a perspective view of a tray configured to hold aplurality of applicators for bulk sterilization and moisture barriersealing, in accordance with some embodiments.

FIG. 28B is a detail view of the tray of FIG. 28A illustrating eachapplicator in a first configuration permeable to a sterilizing gas, anda second configuration impermeable to the sterilizing gas and tomoisture.

FIG. 29 is an exploded perspective view of a sealing element comprisinga first layer permeable to a sterilizing gas and a second layerimpermeable to the sterilizing gas and moisture, in accordance with someembodiments.

FIG. 30A is a zoomed cross-sectional view of a sealing elementcomprising a vent including a material permeable to a sterilizing gas,in accordance with some embodiments.

FIG. 30B is a zoomed cross-sectional view of the sealing element of FIG.30A wherein at least a layer of the vent material is sintered therebybecoming impermeable to the sterilizing gas.

FIG. 31 illustrates a schematic view of a continuous analyte sensorsystem, according to some embodiments.

FIG. 32 is a flowchart illustrating a method of manufacturing anapplicator for applying an on-skin assembly to skin of a host, inaccordance with some embodiments.

FIG. 33 is a flowchart illustrating another method of manufacturing anapplicator for applying an on-skin assembly to skin of a host, inaccordance with some embodiments.

FIG. 34A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a removable cap configuredto seal the applicator, in accordance with some embodiments.

FIG. 34B is a cross-sectional view of the applicator of FIG. 34A.

FIG. 34C is a perspective view of the bottom of the applicator of FIG.34A with a bottom layer.

FIG. 34D is a perspective view of the bottom of the applicator of FIG.34A without a bottom layer.

FIG. 35A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a removable cap configuredto seal the applicator, in accordance with some embodiments.

FIG. 35B illustrates a partially exploded view of the applicator of FIG.35A.

FIG. 36A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a sliding safety lockfeature, in accordance with some embodiments.

FIG. 36B is a perspective view of the applicator of FIG. 36Aillustrating the actuation member in a second state.

FIG. 37A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host with a two state actuation member, inaccordance with some embodiments.

FIG. 37B is a perspective view of the applicator of FIG. 37Aillustrating the actuation member in a second state.

FIG. 38A illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a rotating safety lockfeature, in accordance with some embodiments.

FIG. 38B is a perspective view of the applicator of FIG. 38Aillustrating the actuation member in a second state.

FIG. 39 illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a removable cap releasefeature, in accordance with some embodiments.

FIG. 40 illustrates a perspective view of an applicator for applying anon-skin assembly to skin of a host including a push button safety lockfeature, in accordance with some embodiments.

DETAILED DESCRIPTION OF CERTAIN INVENTIVE EMBODIMENTS

The following description and examples illustrate some exampleembodiments of the disclosed invention in detail. Those of skill in theart will recognize that there are numerous variations and modificationsof this invention that are encompassed by its scope. Accordingly, thedescription of a certain example embodiment should not be deemed tolimit the scope of the present invention.

The present application is directed to embodiments of applicators forapplying an on-skin assembly to skin of a host as well as methods oftheir manufacture and use. As will be described in more detail inconnection with the figures below, certain features of the describedapplicators provide novel and inventive solutions to difficultiesassociated with previous applicator designs and/or methods of their useor manufacture.

System Introduction

U.S. Patent Publication No. US-2013-0267811-A1, the entire contents ofwhich are incorporated by reference herein, explains how FIG. 31 is aschematic of a continuous analyte sensor system 3100 attached to a host(e.g., a person). The analyte sensor system 3100 communicates with otherdevices 3108-3114 (which can be located remotely from the host). Atranscutaneous analyte sensor system 3100 comprising an on-skin sensorassembly 3106 is fastened to the skin of a host via a base (not shown),which can be a disposable housing.

The system 3100 includes a transcutaneous analyte sensor 3102 and anelectronics unit (referred to interchangeably as “sensor electronics” or“transmitter”) 3104 for wirelessly transmitting analyte information to areceiver. The receiver can be located remotely relative to the system3100. In some embodiments, the receiver includes a display screen, whichcan display information to a person such as the host. Example receiversinclude computers such as dedicated display devices, mobile electronics,smartphones, smartwatches, tablet computers, laptop computers, anddesktop computers. In some embodiments, receivers can be Apple Watches,iPhones, and iPads made by Apple Inc. Receivers may be runningcustomized or stock operating systems such as, but not limited to,linux, iOS by Apple Inc., or Android by Google Inc.

In some embodiments, the receiver is mechanically coupled to theelectronics unit 3104 to enable the receiver to receive data (e.g.,analyte data) from the electronics unit 3104. To increase theconvenience to users, in several embodiments, the receiver does not needto be mechanically coupled to the electronics unit 3104 and can evenreceive data from the electronics unit 3104 over great distances (e.g.,when the receiver is many feet or even many miles from the electronicsunit 3104).

During use, a sensing portion of the sensor 3102 can be under the host'sskin and a contact portion of the sensor 3102 can be electricallyconnected to the electronics unit 3104. The electronics unit 3104 can beengaged with a housing (e.g., a base) or directly coupled to an adhesivepatch fastened to the skin of the host.

The on-skin sensor assembly 3106 may be attached to the host with use ofan applicator adapted to provide convenient and secure application. Suchan applicator may also be used for attaching the electronics unit 3104to a base, inserting the sensor 3102 through the host's skin, and/orconnecting the sensor 3102 to the electronics unit 3104. Once theelectronics unit 3104 is engaged with the base and the sensor 3102 hasbeen inserted into the skin (and is connected to the electronics unit3104), the sensor assembly can detach from the applicator.

The continuous analyte sensor system 3100 can include a sensorconfiguration that provides an output signal indicative of aconcentration of an analyte. The output signal including (e.g., sensordata, such as a raw data stream, filtered data, smoothed data, and/orotherwise transformed sensor data) is sent to the receiver.

In some embodiments, the analyte sensor system 3100 includes atranscutaneous glucose sensor, such as is described in U.S. PatentPublication No. US-2011-0027127-A1, the entire contents of which arehereby incorporated by reference. In some embodiments, the sensor system3100 includes a continuous glucose sensor and comprises a transcutaneoussensor (e.g., as described in U.S. Pat. No. 6,565,509, as described inU.S. Pat. No. 6,579,690, as described in U.S. Pat. No. 6,484,046). Thecontents of U.S. Pat. Nos. 6,565,509, 6,579,690, and 6,484,046 arehereby incorporated by reference in their entirety.

In several embodiments, the sensor system 3100 includes a continuousglucose sensor and comprises a refillable subcutaneous sensor (e.g., asdescribed in U.S. Pat. No. 6,512,939). In some embodiments, the sensorsystem 3100 includes a continuous glucose sensor and comprises anintravascular sensor (e.g., as described in U.S. Pat. No. 6,477,395, asdescribed in U.S. Pat. No. 6,424,847). The contents of U.S. Pat. Nos.6,512,939, 6,477,395, and 6,424,847 are hereby incorporated by referencein their entirety.

Various signal processing techniques and glucose monitoring systemembodiments suitable for use with the embodiments described herein aredescribed in U.S. Patent Publication No. US-2005-0203360-A1 and U.S.Patent Publication No. US-2009-0192745-A1, the contents of which arehereby incorporated by reference in their entirety. The sensor canextend through a housing, which can maintain the sensor on the skin andcan provide for electrical connection of the sensor to sensorelectronics, which can be provided in the electronics unit 3104.

One or more repeaters, receivers and/or display devices, such as a keyfob repeater 3108, a medical device receiver 3110 (e.g., an insulindelivery device and/or a dedicated glucose sensor receiver), asmartphone 3112, a portable computer 3114, and the like can becommunicatively coupled to the electronics unit 3104 (e.g., to receivedata from the electronics unit 3104). The electronics unit 3104 can alsobe referred to as a transmitter. In some embodiments, the devices3108-3114 transmit data to the electronics unit 3104. The sensor datacan be transmitted from the sensor electronics unit 3104 to one or moreof the key fob repeater 3108, the medical device receiver 3110, thesmartphone 3112, the portable computer 3114, and the like. In someembodiments, analyte values are displayed on a display device.

The electronics unit 3104 may communicate with the devices 3108-3114,and/or any number of additional devices, via any suitable communicationprotocol. Example communication protocols include radio frequency;Bluetooth; universal serial bus; any of the wireless local area network(WLAN) communication standards, including the IEEE 802.11, 802.15,802.20, 802.22 and other 802 communication protocols; ZigBee; wireless(e.g., cellular) telecommunication; paging network communication;magnetic induction; satellite data communication; and/or a proprietarycommunication protocol.

Additional sensor information is described in U.S. Pat. Nos. 7,497,827and 8,828,201. The entire contents of U.S. Pat. Nos. 7,497,827 and8,828,201 are incorporated by reference herein.

Any sensor shown or described herein can be an analyte sensor; a glucosesensor; and/or any other suitable sensor. A sensor described in thecontext of any embodiment can be any sensor described herein orincorporated by reference, such as an analyte sensor; a glucose sensor;any sensor described herein; and any sensor incorporated by reference.Sensors shown or described herein can be configured to sense, measure,detect, and/or interact with any analyte.

As used herein, the term “analyte” is a broad term, and is to be givenits ordinary and customary meaning to a person of ordinary skill in theart (and is not to be limited to a special or customized meaning), andrefers without limitation to a substance or chemical constituent in abiological fluid (for example, blood, interstitial fluid, cerebralspinal fluid, lymph fluid, urine, sweat, saliva, etc.) that can beanalyzed. Analytes can include naturally occurring substances,artificial substances, metabolites, or reaction products.

In some embodiments, the analyte for measurement by the sensing regions,devices, systems, and methods is glucose. However, other analytes arecontemplated as well, including, but not limited to ketone bodies;Acetyl Co A; acarboxyprothrombin; acylcarnitine; adenine phosphoribosyltransferase; adenosine deaminase; albumin; alpha-fetoprotein; amino acidprofiles (arginine (Krebs cycle), histidine/urocanic acid, homocysteine,phenylalanine/tyrosine, tryptophan); andrenostenedione; antipyrine;arabinitol enantiomers; arginase; benzoylecgonine (cocaine);biotinidase; biopterin; c-reactive protein; carnitine; carnosinase; CD4;ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol;cholinesterase; cortisol; testosterone; choline; creatine kinase;creatine kinase MM isoenzyme; cyclosporin A; d-penicillamine;de-ethylchloroquine; dehydroepiandrosterone sulfate; DNA (acetylatorpolymorphism, alcohol dehydrogenase, alpha 1-antitrypsin, cysticfibrosis, Duchenne/Becker muscular dystrophy, glucose-6-phosphatedehydrogenase, hemoglobin A, hemoglobin S, hemoglobin C, hemoglobin D,hemoglobin E, hemoglobin F, D-Punjab, beta-thalassemia, hepatitis Bvirus, HCMV, HIV-1, HTLV-1, Leber hereditary optic neuropathy, MCAD,RNA, PKU, Plasmodium vivax, sexual differentiation, 21-deoxycortisol);desbutylhalofantrine; dihydropteridine reductase; diptheria/tetanusantitoxin; erythrocyte arginase; erythrocyte protoporphyrin; esterase D;fatty acids/acylglycines; triglycerides; glycerol; free β-humanchorionic gonadotropin; free erythrocyte porphyrin; free thyroxine(FT4); free tri-iodothyronine (FT3); fumarylacetoacetase;galactose/gal-1-phosphate; galactose-1-phosphate uridyltransferase;gentamicin; glucose-6-phosphate dehydrogenase; glutathione; glutathioneperioxidase; glycocholic acid; glycosylated hemoglobin; halofantrine;hemoglobin variants; hexosaminidase A; human erythrocyte carbonicanhydrase I; 17-alpha-hydroxyprogesterone; hypoxanthine phosphoribosyltransferase; immunoreactive trypsin; lactate; lead; lipoproteins ((a),B/A-1, β); lysozyme; mefloquine; netilmicin; phenobarbitone; phenytoin;phytanic/pristanic acid; progesterone; prolactin; prolidase; purinenucleoside phosphorylase; quinine; reverse tri-iodothyronine (rT3);selenium; serum pancreatic lipase; sissomicin; somatomedin C; specificantibodies (adenovirus, anti-nuclear antibody, anti-zeta antibody,arbovirus, Aujeszky's disease virus, dengue virus, Dracunculusmedinensis, Echinococcus granulosus, Entamoeba histolytica, enterovirus,Giardia duodenalisa, Helicobacter pylori, hepatitis B virus, herpesvirus, HIV-1, IgE (atopic disease), influenza virus, Leishmaniadonovani, leptospira, measles/mumps/rubella, Mycobacterium leprae,Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, parainfluenzavirus, Plasmodium falciparum, poliovirus, Pseudomonas aeruginosa,respiratory syncytial virus, rickettsia (scrub typhus), Schistosomamansoni, Toxoplasma gondii, Trepenoma pallidium, Trypanosomacruzi/rangeli, vesicular stomatis virus, Wuchereria bancrofti, yellowfever virus); specific antigens (hepatitis B virus, HIV-1); acetone(e.g., succinylacetone); acetoacetic acid; sulfadoxine; theophylline;thyrotropin (TSH); thyroxine (T4); thyroxine-binding globulin; traceelements; transferrin; UDP-galactose-4-epimerase; urea; uroporphyrinogenI synthase; vitamin A; white blood cells; and zinc protoporphyrin.

Salts, sugar, protein, fat, vitamins, and hormones naturally occurringin blood or interstitial fluids can also constitute analytes in certainembodiments. The analyte can be naturally present in the biologicalfluid or endogenous, for example, a metabolic product, a hormone, anantigen, an antibody, and the like. Alternatively, the analyte can beintroduced into the body or exogenous, for example, a contrast agent forimaging, a radioisotope, a chemical agent, a fluorocarbon-basedsynthetic blood, or a drug or pharmaceutical composition, including butnot limited to insulin; glucagon; ethanol; cannabis (marijuana,tetrahydrocannabinol, hashish); inhalants (nitrous oxide, amyl nitrite,butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine (crackcocaine); stimulants (amphetamines, methamphetamines, Ritalin, Cylert,Preludin, Didrex, PreState, Voranil, Sandrex, Plegine); depressants(barbiturates, methaqualone, tranquilizers such as Valium, Librium,Miltown, Serax, Equanil, Tranxene); hallucinogens (phencyclidine,lysergic acid, mescaline, peyote, psilocybin); narcotics (heroin,codeine, morphine, opium, meperidine, Percocet, Percodan, Tussionex,Fentanyl, Darvon, Talwin, Lomotil); designer drugs (analogs of fentanyl,meperidine, amphetamines, methamphetamines, and phencyclidine, forexample, Ecstasy); anabolic steroids; and nicotine. The metabolicproducts of drugs and pharmaceutical compositions are also contemplatedanalytes. Analytes such as neurochemicals and other chemicals generatedwithin the body can also be analyzed, such as, for example, ascorbicacid, uric acid, dopamine, noradrenaline, 3-methoxytyramine (3MT),3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA),5-hydroxytryptamine (5HT), 5-hydroxyindoleacetic acid (FHIAA), andintermediaries in the Citric Acid Cycle.

Many embodiments described herein use an adhesive. One purpose of theadhesive can be to couple a base, a sensor module, and/or a sensor to ahost (e.g., to skin of the host). The adhesive can be configured foradhering to skin. The adhesive can include a pad (e.g., that is locatedbetween the adhesive and the base). Additional adhesive information,including adhesive pad information, is described in U.S. patentapplication Ser. No. 14/835,603, which was filed on Aug. 25, 2015. Theentire contents of U.S. patent application Ser. No. 14/835,603 areincorporated by reference herein.

Sterilization and Sealing of Applicators

Any time a foreign structure comes in contact with the human body thereis a potential for infection, which can lead to serious healthconsequences. Thus, sterilization of an applicator (and/or of theportions of an applicator that come in contact with, or that areinserted into, a body part of the host) are not only desirable, butrequired in many circumstances. Various sterilization methods can beused in embodiments, including but not limited to heat sterilization,gamma sterilization, electron beam sterilization, and gas (e.g. ethyleneoxide) sterilization. In embodiments adapted for gas sterilization, anapplicator can be configured with one or more apertures, at least duringone or more steps of manufacture, which are configured to allow ingressand egress of gas during one or more sterilization steps. In addition,it may be desirable to seal applicators from ingress of moisture (e.g.,water vapor) in some embodiments. Moisture, especially water vapor, cancorrode (e.g., rust, tarnish) any metallic parts within an applicator,for example, a needle, a spring, or any other metallic structure. Suchcorrosion coming in contact with the host, especially where a needleenters the skin of a host, can cause serious health consequences.Moisture can also promote growth of infectious agents and provide amedium for their proliferation, causing serious health consequences. Thepresent application provides various embodiments of applicators that aregas sterilizable and/or include a moisture (e.g., water vapor) seal, forexample, through the use of one or more removable caps on the top (e.g.,proximal) or bottom (e.g., distal) ends of the applicator, through oneor more trigger mechanisms comprising integrated caps, through one ormore sealing layers that cover one or more orifices, apertures or ventsof the applicator, through sterilizable gas-permeable polymers, throughsterilizable gas-permeable trigger mechanisms, through protective cups,or any combinations of the same, as will be described in more detail inconnection with at least some of FIGS. 1A-40 below.

Safety Features of Applicators

Consumers may find it desirable to use applicators that provideparticular safety features. For example, tamper evident sealing or othertamper evidence features may be desirable because such features allow aconsumer to identify when an applicator has been previously used orcontainment has been breached and, thus, avoid using an applicator thatmay be faulty or pose an increased health risk if used. Examples oftamper evidence features are described in more detail in connection withat least some of FIGS. 1A-40 below.

In addition, especially in the case of disposable applicators, it can befrustrating or dangerous to have an applicator deploy prematurely orunexpectedly. Thus, consumers may find it desirable for applicators toinclude premature deployment prevention features to substantially reduceor prevent the occurrence of premature activation. Examples of prematuredeployment prevention features are described in more detail inconnection with at least some of FIGS. 1A-40 below.

In line with premature deployment prevention features, it may bedesirable to provide features which minimize the risk of unintendedactivation when the applicator is dropped. For example, an exposedtrigger mechanism may be accidentally activated if the applicator isdropped on the exposed trigger mechanism. However, in some cases, theshock of dropping the applicator itself can cause accidental activationof the applicator even where there is no exposed trigger mechanism.Examples of drop protection features and other premature deploymentprevention features are described in more detail in connection with atleast some of FIGS. 1A-40 below.

Bulk Manufacturing and/or Sterilization

The cost of manufacture of applicators is a concern for the manufactureras well as for the consumer. In general, the less expensive it is toproduce an applicator, the lower the cost it is to the consumer. Thus,it is desirable to provide bulk manufacturing, sterilizing and/orsealing of applicators. Examples of applicator configurations andmethods of bulk sterilizing and/or sealing of applicators include, butare not limited to, melting, chemically altering, or physically alteringa vent, plug, feature, or layer such that it transforms from a state ofbeing permeable to a sterilizing gas and/or moisture (e.g., water vapor)to impermeable to the sterilizing gas and/or moisture, as will bedescribed in more detail in connection with at least some of FIGS. 1A-40below.

Easy and Repositionable Deployment

Consumers may additionally find it desirable to easily position (andreposition if desired) an applicator in a particular location on thebody, optionally using only a single hand, without necessarily requiringa complete view of the applicator as it is held in the desired location.Such easy single-handed deployment may be achieved through the provisionof various orientations and forms of actuation members, as well as theuse of one or more raised or recessed portions configured as tactilegrips and/or orientation indicators, as will be described in more detailin connection with at least some of FIGS. 1A-40 below. Consumers mayalso find it desirable to be able to reposition the applicator prior toactivation even after it has been first placed on the body, withoutcomprising the integrity of the applicator and/or any adhesive providedthereon.

Embodiments Including a Removable Cap

Some embodiments can include a removable cap configured to function as asterilization seal and/or as a moisture barrier. For example, FIG. 1A isan exploded, cutaway view of an applicator 100 for applying an on-skinassembly 102 to skin of a host including a sealing element 110, inaccordance with some embodiments. Applicator 100 comprises a housing 104configured to house an insertion assembly 118 (see FIG. 1B). Housing 104comprises an aperture 106 through which on-skin assembly 102 (see FIG.1B) is configured to pass during deployment. The side of housing 104 mayfurther comprise an opening 120 configured to receive an actuationmember (not shown in FIGS. 1A-1C). Such an actuation member can beconfigured to, upon activation, cause insertion assembly 118 to insertat least a portion of on-skin assembly 102 into the skin of a host. Theactuation member is disposed on a side of housing 104 in the region ofthe opening 120. By providing an actuation member on a side of housing104, applicator 100 may provide for easy single-handed deployment ofon-skin assembly 102 to the skin of a host.

Housing 104 further comprises an optional flexible wall 128 configuredto absorb at least a portion of energy imparted to applicator 100 whenapplicator 100 is dropped. By absorbing energy that might otherwisetransfer a physical shock to applicator 100, flexible wall 128 mayprovide a premature deployment prevention and drop protection feature.

Applicator 100 further comprises a sealing element 110 configured toprovide a sterile barrier and/or a vapor barrier between an internalenvironment of housing 104 and an external environment of housing 104.As shown in FIG. 1A, sealing element 110 comprises a removable cap 112configured to couple with a portion of housing 104. Specifically, and asan example, removable cap 112 is configured to couple with a distalportion of housing 104 via threads 114. For example, threads 114disposed on removable cap 112 may be configured to mate with threads 108disposed on housing 104. Removable cap 112 may be detached from housing104 by twisting removable cap 112 with respect to housing 104, or viceversa, until threads 114 and threads 108 are no longer mated with eachother, and then pulling housing 104 and removable cap 112 apart. Sealingelement 110 may additionally comprise retention element 138 betweenremovable cap 112 and housing 104 before removal of removable cap 112.As shown, removable cap 112 covers the actuation member by virtue of theactuation member being disposed on a side of housing 104. Sealingelement 110 may further comprise a first layer 122 that is permeable toa sterilizing gas (e.g., ethylene oxide, or ETO). First layer 122 maycomprise Tyvek® material, although any other material permeable to asterilizing gas may be utilized. Application of first layer 122 toremovable cap 112 may allow for the ingress and egress of a sterilizinggas during manufacture. Sealing element 110 may further comprise asecond layer 124 that is substantially impermeable to moisture (e.g.,water vapor). Second layer 124 may comprise a metallic foil, althoughany suitable material impermeable to moisture (e.g., water vapor) may beutilized, for example, a metallic foil (e.g., aluminum or titanium), ametallic substrate, an aluminum oxide coated polymer, parylene, apolymer coated with a metal applied via vapor metallization, a silicondioxide coated polymer, or any material having a moisture vaportransmission rate less than 10 grams/100 in² or preferably less than 1gram/100 in². First layer 122 and second layer 124 may seal an opening126 in the bottom of removable cap 112. Application of second layer 124over first layer 122 after sterilization may further maintain sterilityvia the first layer and add a moisture barrier via the second layer.Together, the above-described features of sealing element 110 mayprovide joint sterilization and moisture sealing of applicator 100.

The applicator 100 further includes a support member 116 configured toinhibit at least lateral movement of insertion assembly 118. In someembodiments, support member 116 may comprise an elastomeric membrane,film, bulk elastomer, foam, or rigid structure. Furthermore, supportmember 116 can maintain the insertion assembly 118 in position duringdeleterious movement such as a drop or vibration.

FIG. 1B is a zoomed cutaway view of applicator 100 of FIG. 1A, furtherillustrating at least insertion assembly 118 and on-skin assembly 102,in accordance with some embodiments. As shown in more detail in FIG. 1B,insertion assembly 118 may comprise a needle 140, for example, aC-needle configured to hold at least a portion of a sensor. In someembodiments, insertion assembly 118 may be configured to drive needle140 utilizing a spring force. In some embodiments, insertion assembly118 may additionally or alternatively be configured to retract needle140 after on-skin assembly 102 has been deployed to the skin of thehost.

In some embodiments, insertion assembly 118 may include substantiallysimilar components and/or mechanisms from insertion assembly 118 of FIG.8A-8C. In other embodiments, insertion assembly 118 may includesubstantially similar components from insertion assemblies described inU.S. patent application Ser. No. 15/387,088, which is incorporatedherein by reference it its entirety. For non-limiting example, insertionassembly 118 may include substantially similar components and/ormechanisms from telescoping assembly 132 of FIGS. 7-11, telescopingassembly 132b of FIGS. 56-58, telescoping assembly 132c and 132d ofFIGS. 28-30, telescoping assembly 132e of FIG. 31, telescoping assembly132f of FIG. 59, telescoping assembly 132g of FIGS. 44-45, telescopingassembly 132h of FIG. 60, telescoping assembly 132i of FIG. 48-50,telescoping assembly 132k of FIGS. 61-64, telescoping assembly 132m ofFIGS. 71-74, telescoping assembly 132n of FIGS. 76-79, telescopingassembly 132p of FIGS. 80-85, telescoping assembly 132q of FIGS. 86-88,telescoping assembly 132r of FIGS. 89-91, telescoping assembly 132s ofFIGS. 92-100, or telescoping assembly 132w of FIGS. 110-119,respectively described in U.S. patent application Ser. No. 15/387,088.

Applicator 100 further comprises a transcutaneous on-skin analyte sensorassembly (referred to as an “on-skin assembly”) 102 and an electronicsunit (referred to as a “transmitter”) 134 for wirelessly transmittinganalyte information to a receiver (not shown). Before deployment, asensor 132 of on-skin assembly 102 may be disposed on or at leastpartially in needle 140. During use, sensor 132 is disposed under thehost's skin and a contact portion of on-skin assembly 102 iselectrically connected to transmitter 134. On-skin assembly 102 isattached to an adhesive layer 136 for fastening to the skin of the host.

On-skin assembly 102 may be attached to the host with use of applicator100 adapted to provide convenient and secure application. Applicator 100may also be used for inserting at least a portion of on-skin assembly102 through the host's skin. Once the portion of on-skin assembly 102has been inserted, applicator 100 detaches from on-skin assembly 102.

In general, on-skin assembly 102 includes any sensor configuration thatprovides an output signal indicative of a concentration of an analyte,for example, blood glucose. The output signal including, e.g., sensordata, such as a raw data stream, filtered data, smoothed data, and/orotherwise transformed sensor data, is sent to a receiver which may bee.g., a smart phone, smart watch, dedicated device and the like. In someembodiments, sensor 132 comprises a transcutaneous glucose sensor, suchas is described in US Patent Publication No. US-2011-0027127-A1, thecontents of which are hereby incorporated by reference in its entirety.In some embodiments, sensor 132 is a continuous glucose sensor andcomprises a transcutaneous sensor such as described in U.S. Pat. No.6,565,509 to Say et al., for example. In another embodiment, sensor 132is a continuous glucose sensor and comprises a subcutaneous sensor suchas described with reference to U.S. Pat. No. 6,579,690 to Bonnecaze etal. or U.S. Pat. No. 6,484,046 to Say et al., for example. In some otherembodiments, sensor 132 is a continuous glucose sensor and comprises asubcutaneous sensor such as described with reference to U.S. Pat. No.6,512,939 to Colvin et al. In yet other embodiments, sensor 132 is acontinuous glucose sensor and comprises an intravascular sensor such asdescribed with reference to U.S. Pat. No. 6,477,395 to Schulman et al.,for example. In yet other embodiments, sensor 132 is a continuousglucose sensor and comprises an intravascular sensor such as describedwith reference to U.S. Pat. No. 6,424,847 to Mastrototaro et al. Othersignal processing techniques and glucose monitoring system embodimentssuitable for use with the embodiments described herein are described inU.S. Patent Publication No. US-2005-0203360-A1 and U.S. PatentPublication No. US-2009-0192745-A1, the contents of which are herebyincorporated by reference in their entireties.

In still further embodiments, applicator 100 can be configured for usein applying a drug delivery device, such an infusion device, to the skinof a patient. In such embodiments, applicator 100 can include a catheterinstead of, or in addition to, a sensor, the catheter being connected toan infusion pump configured to deliver liquid medicines or other fluidsinto the patient's body. In embodiments, the catheter can be deployedinto the skin in much the same manner as a sensor would be, for exampleas described herein.

In some embodiments, sensor 132 is formed from a wire or is in a form ofa wire. For example, sensor 132 can include an elongated conductivebody, such as a bare elongated conductive core (e.g., a metal wire) oran elongated conductive core coated with one, two, three, four, five, ormore layers of material, each of which may or may not be conductive. Theelongated sensor may be long and thin, yet flexible and strong. Forexample, in some embodiments, the smallest dimension of the elongatedconductive body is less than about 0.1 inches, less than about 0.075inches, less than about 0.05 inches, less than about 0.025 inches, lessthan about 0.01 inches, less than about 0.004 inches, or less than about0.002 inches. Sensor 132 may have a circular cross-section. In someembodiments, the cross-section of the elongated conductive body can beovoid, rectangular, triangular, polyhedral, star-shaped, C-shaped,T-shaped, X-shaped, Y-Shaped, irregular, or the like. In someembodiments, a conductive wire electrode is employed as a core. To sucha clad electrode, one or two additional conducting layers may be added(e.g., with intervening insulating layers provided for electricalisolation). The conductive layers can be comprised of any suitablematerial. In certain embodiments, it can be desirable to employ aconductive layer comprising conductive particles (i.e., particles of aconductive material) in a polymer or other binder.

In certain embodiments, the materials used to form the elongatedconductive body (e.g., stainless steel, titanium, tantalum, platinum,platinum-iridium, iridium, certain polymers, and/or the like) can bestrong and hard, and therefore are resistant to breakage. For example,in some embodiments, the ultimate tensile strength of the elongatedconductive body is from about 80 kPsi to about 500 kPsi. In anotherexample, in some embodiments, the Young's modulus of the elongatedconductive body is from about 160 GPa to about 220 GPa. In still anotherexample, in some embodiments, the yield strength of the elongatedconductive body is from about 60 kPsi to about 2200 kPsi. In someembodiments, sensor's 132 small diameter provides (e.g., imparts,enables) flexibility to these materials, and therefore to sensor 132 asa whole. Thus, sensor 132 can withstand repeated forces applied to it bysurrounding tissue.

In addition to providing structural support, resiliency and flexibility,in some embodiments, the core (or a component thereof) provideselectrical conduction for an electrical signal from the workingelectrode to sensor electronics (not shown). In some embodiments, thecore comprises a conductive material, such as stainless steel, titanium,tantalum, a conductive polymer, and/or the like. However, in otherembodiments, the core is formed from a non-conductive material, such asa non-conductive polymer. In yet other embodiments, the core comprises aplurality of layers of materials. For example, in some embodiments thecore includes an inner core and an outer core. In a further embodiment,the inner core is formed of a first conductive material and the outercore is formed of a second conductive material. For example, in someembodiments, the first conductive material is stainless steel, titanium,tantalum, a conductive polymer, an alloy, and/or the like, and thesecond conductive material is conductive material selected to provideelectrical conduction between the core and the first layer, and/or toattach the first layer to the core (e.g., if the first layer is formedof a material that does not attach well to the core material). Inanother embodiment, the core is formed of a non-conductive material(e.g., a non-conductive metal and/or a non-conductive polymer) and thefirst layer is a conductive material, such as stainless steel, titanium,tantalum, a conductive polymer, and/or the like. The core and the firstlayer can be of a single (or same) material, e.g., platinum. One skilledin the art appreciates that additional configurations are possible.

In some embodiments, transmitter 134 is incorporated into on-skinassembly 102, while in other embodiments, the transmitter 134 can bereleasably coupled to the sensor. Transmitter 134 includes electroniccircuitry associated with measuring and processing the continuousanalyte sensor data, and is configured to perform algorithms associatedwith processing and calibration of the sensor data. For example,transmitter 134 can provide various aspects of the functionality of asensor electronics module as described in U.S. Patent Publication No.2009-0240120-A1 and U.S. Patent Publication No. 2012-0078071-A1 thecontents of which are hereby incorporated by reference in theirentireties. Transmitter 134 may include hardware, firmware, and/orsoftware that enable measurement of levels of the analyte via a glucosesensor, such as an analyte on-skin assembly 102. For example,transmitter 134 can include a potentiostat, a power source for providingpower to on-skin assembly 102, other components useful for signalprocessing and data storage, and preferably a telemetry module for one-or two-way data communication between transmitter 134 and one or morereceivers, repeaters, and/or display devices. Electronics can be affixedto a printed circuit board (PCB), or the like, and can take a variety offorms. For example, the electronics can take the form of an integratedcircuit (IC), such as an Application-Specific Integrated Circuit (ASIC),a microcontroller, and/or a processor. Transmitter 134 may includesensor electronics that are configured to process sensor information,such as storing data, analyzing data streams, calibrating analyte sensordata, estimating analyte values, comparing estimated analyte values withtime corresponding measured analyte values, analyzing a variation ofestimated analyte values, and the like. Examples of systems and methodsfor processing sensor analyte data are described in more detail hereinand in U.S. Pat. Nos. 7,310,544, 6,931,327, U.S. Patent Publication No.2005-0043598-A1, U.S. Patent Publication No. 2007-0032706-A1, U.S.Patent Publication No. 2007-0016381-A1, U.S. Patent Publication No.2008-0033254-A1, U.S. Patent Publication No. 2005-0203360-A1, U.S.Patent Publication No. 2005-0154271-A1, U.S. Patent Publication No.2005-0192557-A1, U.S. Patent Publication No. 2006-0222566-A1, U.S.Patent Publication No. 2007-0203966-A1 and U.S. Patent Publication No.2007-0208245-A1, the contents of which are hereby incorporated byreference in their entireties.

One or more repeaters, receivers and/or display devices, such as amedical device receiver (e.g., insulin delivery device and/or dedicatedglucose sensor receiver), smart phone, portable computer, and the likemay be operatively linked to and receive data from transmitter 134, andin some embodiments transmit data to transmitter 134.

In some embodiments, analyte values are displayed on a display device.In some embodiments, prompts or messages can be displayed on the displaydevice to convey information to the user, such as reference outliervalues, requests for reference analyte values, therapy recommendations,deviation of the measured analyte values from the estimated analytevalues, or the like. Additionally, prompts can be displayed to guide theuser through calibration or trouble-shooting of the calibration.

Although not necessarily shown in other FIGs., any applicator describedin this specification may include insertion assembly 118 and on-skinassembly 102 as described in connection with FIGS. 1A and 1B.

Applicator 100 may further comprise a tamper indicator 130,specifically, a tamper-evident ring configured to break away fromremovable cap 112 when removable cap 112 is twisted with respect tohousing 104. In this way, tamper indicator 130 may provide a safetyfeature for a host using applicator 100 such that if the tamper-evidentring is broken, tampering would be visually evident to a user.

FIG. 1C illustrates another applicator 150 for applying on-skin assembly102 to skin of a host including a sealing element 160 having a frangiblemember 164, in accordance with some other embodiments. Applicator 150may comprise all features previously described in connection withapplicator 100 of FIGS. 1A and 1B except, instead of utilizing threads114 and 108, sealing element 160 comprises a removable cap 162configured to couple with a distal portion of housing 104 via frangiblemember 164. In some embodiments, frangible member 164 comprises a loopand a circumferential frangible portion configured to be removed bypulling on the loop. In this way, sealing element 160, includingremovable cap 162 and frangible member 164, may maintain sterilizationand simultaneously provide a moisture seal for elements within housing104. Frangible member 164 may prevent sealing cap 162 from being removedwithout also removing frangible member 164. Frangible member 164 furtherprovides a tamper indicator and safety feature for a host usingapplicator 150 such that if the frangible member 164 is broken,tampering would be visually evident to a user.

FIG. 2A illustrates a perspective view of an applicator 200 for applyingon-skin assembly 102 to skin of a host including a peelable tamperindicator 230, in accordance with some embodiments. Applicator 200 maycomprise all features previously described in connection with applicator100 of FIGS. 1A and 1B except those specifically indicated as not beingpresent below. For example, although not shown, applicator 200 mayfurther include at least insertion assembly 118 and on-skin assembly 102as described in connection with FIGS. 1A-1C.

Applicator 200 comprises a housing 204, a sealing element 210 comprisinga removable cap 212, and peelable tamper indicator 230. Housing 204 maynot include flexible wall 128 or threads 108 as previously described inconnection with FIGS. 1A and 1B Likewise, removable cap 212 may notinclude threads 114. However, removable cap 212 may comprise at leastone protrusion 220 or flattened (e.g., substantially planar) sectionconfigured to inhibit rolling of applicator 200 and to provide anorientation indicator for the user. Removable cap 212 may be detachedfrom housing 204 by peeling off peelable tamper indicator 230 andpulling apart removable cap 212 and housing 204. Thus, if peelabletamper indicator 230 has been disturbed, tampering would be visuallyevident to a user.

FIG. 2B is a partially exploded view of applicator 200 of FIG. 2A. Asshown more clearly in FIG. 2B, applicator 200 may further comprise anactuation member 250 (e.g., a push button) configured to, uponactivation, cause insertion assembly 118 (see FIG. 1B) to insert atleast a portion of on-skin assembly 102 (see FIG. 1B) into the skin of ahost through aperture 106. Similar to FIGS. 1A-1C, removable cap 212covers actuation member 250 by virtue of actuation member 250 beingdisposed on a side of housing 204 and removable cap 212 covering adistal portion of housing 204 which shrouds actuation member 250.Shrouding actuation member 250 in this manner may prevent accidentalactivation. Sealing element 210 may further comprise first layer 122 andsecond layer 124, as previously described in connection with FIG. 1B.First layer 222 and second layer 224 may be disposed over one or moreopenings 226 in the bottom of removable cap 212. In some embodiments,the one or more openings 226 facilitate in sterilization and/or ventingof the applicator 200. The above-described features of sealing element210 may provide joint sterilization and moisture sealing for applicator200.

FIG. 3A illustrates a perspective view of an applicator 300 for applyingon-skin assembly 102 to skin of a host including a perforated tamperindicator tab 330, in accordance with some embodiments. Applicator 300may comprise all features previously described in connection withapplicator 100 of FIGS. 1A and 1B except those specifically indicated asnot being present below. For example, although not shown, applicator 300may further include at least insertion assembly 118 and on-skin assembly102 as described in connection with FIGS. 1A-1C.

Applicator 300 comprises a housing 304, a sealing element 310 comprisingat least a removable cap 312, and adhesive mounted tamper indicator tab330. Tamper indicator tab 330 may be adhesively backed paper, polymer,or other compatible film material. The tamper indicator tab 330 mayfurther contain perforations, scoring, or deformed sections to guideremoval of the tamper indicator tab 330. Housing 304 is further shown toinclude optional flexible wall 128 but may not include threads 108 aspreviously described in connection with FIGS. 1A and 1B. Likewise,removable cap 312 may not include threads 114. Removable cap 312 may bedetached from housing 304 by twisting and pulling apart removable cap312 and housing 304. Any tampering with applicator 300 may result in thebreaking of tamper indicator tab 330, providing visual evidence oftampering to a user.

FIG. 3B is a zoomed cutaway view of applicator 300 of FIG. 3A, inaccordance with some embodiments. As shown, removable cap 312 and/orhousing 304 may comprise retention element 138 as previously describedin connection with FIGS. 1A and 1B. Sealing element 310 may furthercomprise an O-ring 340 configured to provide a seal between removablecap 312 and housing 304. In some embodiments, O-ring 340 may beintegrally molded together with either cap 312 or housing 304.

FIG. 3C is another zoomed cutaway view of applicator 300 of FIGS. 3A and3B, in accordance with some embodiments. As shown, the side of housing304 may further comprise opening 120 configured to receive an actuationmember (not shown in FIGS. 3A-3C), as previously described in connectionwith FIGS. 1A and 1B. By providing an actuation member on a side ofhousing 304, applicator 300 may provide for easy single-handeddeployment of on-skin assembly 102 (not shown in FIG. 3C) to the skin ofa host.

FIG. 3C further illustrates opening 126 in the bottom of removable cap312, as previously described in connection with FIGS. 1A and 1B.Although not shown, sealing element 310 may further comprise first layer122 and second layer 124 covering opening 126, as previously describedin connection with FIGS. 1A and 1B. Together, the above-describedfeatures of sealing element 310 may provide joint sterilization andmoisture sealing of applicator 100.

FIG. 4A illustrates another applicator 400 for applying on-skin assembly102 to skin of a host including a tamper indicator tab 330, inaccordance with some embodiments. FIG. 4B is a partially exploded viewof applicator 400 of FIG. 4A. Applicator 400 comprises substantiallysimilar features of applicator 200 of FIGS. 2A and 2B, however,replacing peelable tamper indicator 230 with tamper indicator tab 330 ofFIGS. 3A-3C. As shown in FIG. 4B, applicator 400 may comprise the one ormore openings 226 in the bottom of removable cap 212, as previouslydescribed in connection with at least FIG. 2B. First layer 122 andsecond layer 124 may cover the one or more openings 226.

FIG. 5A illustrates another applicator 500 for applying on-skin assembly102 to skin of a host including a tactile indication of grip for thehost, in accordance with some embodiments. FIG. 5B is a partiallyexploded view of applicator 500 of FIG. 5A. Applicator 500 comprisessubstantially all features of applicator 200 of FIGS. 2A and 2B,however, replacing peelable tamper indicator 230 with a tamper-evidenttwist-off collar 530 and further including at least one set of one ormore ridges or recesses 542, 544 configured to provide a tactileindication of grip to the host. For example, FIGS. 5A and 5B show ahousing 504, which may be substantially the same as housing 204 of FIGS.2A and 2B, however, further including a first set of one or more ridgesor recesses 542 configured to provide a tactile indication of grip tothe host. FIGS. 5A and 5B further show a removable cap 512, which may besubstantially the same as removable cap 212, however, further includinga second set of one or more ridges or recesses 544 configured to providea tactile indication of grip to the host. As shown in FIG. 5BB,applicator 500 may comprise the one or more openings 226 in the bottomof removable cap 212, as previously described in connection with atleast FIG. 2B. First layer 122 and second layer 124 may cover the one ormore openings 226.

In addition, tamper-evident twist-off collar 530 is disposed at a matinglocation between housing 504 and removable cap 512. In some embodiments,a first portion 530 a of tamper-evident twist-off collar 530 may becoupled to removable cap 512 and a second portion 530 b oftamper-evident twist-off collar 530 may be coupled to housing 504.Removable cap 512 may be detached from housing 504 by twisting removablecap 512 with respect to housing 504, or vice versa, until first portion530 a breaks free of second portion 530 b, and then pulling removablecap 512 and housing 504 apart. In its integral state, tamper-evidenttwist-off collar 530 may provide a seal (e.g., a sterile barrier and amoisture or water vapor barrier) between housing 504 and removable cap512. In its separated state, tamper-evident twist-off collar 530 mayprovide an indication of tampering to a user.

FIG. 6A illustrates another applicator 600 for applying on-skin assembly102 to skin of a host including a removable cap 612 configured to couplewith a housing 604 in a single axial orientation, in accordance withsome embodiments. FIG. 6B is a partially exploded view of applicator 600of FIG. 6A. Applicator 600 comprises substantially all features ofapplicator 200 of FIGS. 2A and 2B, however, not including peelabletamper indicator 230, including a removable cap 612 and a housing 604both having shapes that couple in a single axial orientation and whencombined limit rotation about the axis, and further including at leastone set of one or more ridges or recesses 642, 644 configured to providea tactile indication of grip to the host.

For example, FIGS. 6A and 6B show housing 604, which may besubstantially the same as housing 204 of FIGS. 2A and 2B, however,further including a first set of one or more ridges or recesses 642configured to provide a tactile indication of grip to the host. Housing604 may also include a visual indicator 608 located on a surface ofhousing 604 (as shown located on the top surface). Visual indicator 608may be a slight protrusion or a slight indentation from the surface ofthe housing 604. Furthermore, visual indicator 608 may have a shapesimilar to the shape of the on-skin assembly 102. The orientation ofvisual indicator 608 may match with the orientation of on-skin assembly102 within applicator 600. As such, visual indicator 608 may assist inorienting the user to the orientation of the on-skin assembly 102 withinthe applicator 600 prior to deployment.

Housing 604 further has an irregularly shaped mating edge 652 that isnot planar such that housing 604 will properly mate with removable cap612 in a single axial orientation. Likewise, FIGS. 6A and 6B furthershow removable cap 612, which may be substantially the same as removablecap 212, however, further including a second set of one or more ridgesor recesses 644 configured to provide a tactile indication of grip tothe host. Removable cap 612 further has an irregularly shaped matingedge 654 that is complementary in shape to the mating edge of housing604 such that removable cap 612 will properly mate with housing 604 inthe single axial orientation. Removable cap 612 may be detached fromhousing 604 by twisting removable cap 612 with respect to housing 604,or vice versa, and then pulling removable cap 612 and housing 604 apart.In some embodiments, the irregularly shaped mating edges 652, 654 ofhousing 604 and removable cap 612 also function as a tamper indication,since any tampering that causes relative displacement in any directionbetween removable cap 612 and housing 604 would cause their separation,thereby providing visual indication of tampering.

Embodiments Including a Top Cap Actuation member

Some embodiments can include an actuation member which is coupled to, orintegrally formed with, a removable cap. For example, FIG. 7Aillustrates a perspective view of an applicator 700 for applying on-skinassembly 102 to skin of a host including a frangible member as a safetyconfigured to prevent activation of an actuation member, in accordancewith some embodiments. FIG. 7B is a partially exploded view ofapplicator 700 of FIG. 7A. Although not shown, applicator 700 mayfurther include insertion assembly 118 and on-skin assembly 102 asdescribed in connection with FIGS. 1A-1C and as will be furtherdescribed in connection with FIGS. 8B and 8C below.

Applicator 700 comprises a housing 704 configured to house insertionassembly 118 (not shown) and comprises aperture 106 through whichon-skin assembly 102 can pass. Housing 704 further comprises a vent 762configured to be permeable to a sterilizing gas and able to maintain asterile barrier. In some embodiments, vent 762 may be disposed on a top(i.e., proximal) side of housing 704. In some embodiments, a porouspolymeric component is inserted into vent 762, for example, a Porex®plug. In some embodiments, second layer 124, as previously described inconnection with FIGS. 1A and 1B, may be disposed directly over aperture106 after sterilization, thereby providing a moisture barrier at thedistal portion of housing 704.

In some embodiments, insertion assembly 118 and on-skin assembly 102(not shown in detail in FIG. 7B) may be disposed within housing 704 andthen second layer 124 may be disposed over aperture 106, thereby sealingthe distal portion of housing 704. Ingress and egress of a sterilizinggas may then be achieved through vent 762, after which a sealing layer764 may be disposed over vent 764 and a proximal portion of housing 704,thereby completely sealing an inside of housing 704 from an outsideenvironment. Accordingly, in some embodiments, the combination of atleast housing 704, second layer 124 and sealing layer 764 may form asealing element configured to provide a sterile barrier and a vaporbarrier between an internal environment and an external environment ofhousing 704.

Applicator 700 further comprises an actuation member 750 comprising atelescoping cap coupled to the proximal portion of housing 704.Accordingly, sealing layer 764 is disposed between the actuation member750 (i.e., the cap) and housing 704. Actuation member 750 is configuredto be activated by moving the cap in a distal direction. Accordingly,actuation member 750 may further comprise a protrusion 752 configured topierce sealing layer 764 and thereby activate insertion assembly 118(not shown) within housing 704 when the cap is moved in the distaldirection. In some embodiments, actuation member 750 may be springloaded such that pressure exceeding a threshold is required in order tomove the cap in the distal direction sufficiently to activate actuationmember 750.

Applicator 700 may further comprise a frangible safety member 766configured to prevent activation of actuation member 750. In someembodiments, frangible safety member 766 is disposed between actuationmember 750 and a distal portion of housing 704 such that frangiblesafety member 766 physically prevents movement of actuation member 750at least until frangible safety member 766 is removed or sufficientlydisplaced. In this way, frangible safety member 766 simultaneouslyprovides a premature deployment feature, a drop protection feature, anda tamper indication.

FIG. 8A illustrates another applicator 800 for applying on-skin assembly102 to skin of a host including another frangible safety member 866configured to prevent activation of an actuation member 850, inaccordance with some embodiments. Applicator 800 is substantially thesame as application 700 previously described in connection with FIGS. 7Aand 7B, however, including a few similar features having slightlydifferent shapes, excluding vent 764, and further illustrating a fewadditional features as described below.

For example, applicator 800 is shown to include housing 704 and secondlayer 124 as previously described in connection with FIGS. 7A and 7B.Applicator 800 further comprises a frangible safety member 866 havingsubstantially the same function and location as frangible safety member766 of FIGS. 7A and 7B, however, having a substantially horizontalorientation rather than a substantially vertical orientation. Applicator800 further comprises actuation member 850 comprising a telescoping capcoupled to the proximal portion of housing 704 and having substantiallythe same function as actuation member 750 but with a slightly differentshape.

FIG. 8B is a cutaway view of applicator 800 of FIG. 8A in apre-deployment configuration. FIG. 8B further illustrates insertionassembly 118 disposed within housing 704 and sealing layer 764. However,applicator 800 omits vent 764 and sealing layer 764 is instead disposedover an opening in a proximal portion of housing 704. Accordingly, insome embodiments, insertion assembly 118 and on-skin assembly 102 may bedisposed within housing 704 and then second layer 124 may be disposedover aperture 106, thereby sealing the distal portion of housing 704.Ingress and egress of a sterilizing gas may then be achieved through theopening in the proximal portion of housing 704, after which sealinglayer 764 may be disposed over the opening and over the proximal portionof housing 704, thereby completely sealing an inside of housing 704 froman outside environment. Accordingly, in some embodiments, thecombination of at least housing 704, second layer 124 and sealing layer764 may form a sealing element configured to provide a sterile barrierand a vapor barrier between an internal environment and an externalenvironment of housing 704.

FIG. 8B further illustrates protrusion 752 of actuation member 850 in aposition ready to pierce sealing layer 764 when actuation member 850(e.g., telescoping cap) is moved in a distal direction. Applicator 800is further illustrated as including a spring feature 854 (e.g. molded orintegrated spring feature) configured to provide the biased force loadedaspect of the actuation member 850 as previously described in connectionwith FIGS. 7A and 7B.

FIG. 8C is a cutaway view of applicator 800 of FIG. 8A in a deployedconfiguration. As shown, second layer 124 has been removed beforedeployment and actuation member 850 is shown as having been moved in thedistal direction, causing protrusion 752 to pierce sealing layer 764 andactivate insertion assembly 118.

FIG. 9A illustrates another applicator 900 for applying on-skin assembly102 to skin of a host including an actuation member 950 configured as acap disposed over housing 704 of applicator 900, in accordance with someembodiments. Applicator 900 is substantially similar to applicator 800previously described in connection with FIGS. 8A-8C, except as describedbelow. As shown in FIG. 9A, applicator 900 includes housing 704, secondlayer 124 sealing aperture 106 (not shown) of housing 704 and sealinglayer 764 disposed on proximal portion of housing 704. Applicator 900further comprises actuation member 950 comprising a cap coupled to theproximal portion of housing 704. Actuation member 950 comprisesprotrusion 752, which is configured to pierce sealing layer 764 duringactivation of actuation member 950. The cap forming actuation member 950may further comprise a side flexure 956 configured to unlock actuationmember 950. Specifically, moving side flexture 956 allows the actuationmember 950 to move in a distal direction arms. Activation member 950further moves protrusion 752 such that it pierces sealing layer 764 andactivates insertion assembly 118 (not shown, see FIGS. 8B and 8C).Furthermore, applicator 900 may not include spring feature 854, butinstead comprises a spring feature 954 disposed on a side of housing 704between housing 704 and the cup of actuation member 950, which mayprovide substantially the same effect as spring feature 854. In someembodiments, spring feature 954 may be coupled to housing 704 at one endand coupled to the cup forming actuation member 950 at the other end.Actuation member 950 may provide additional premature deploymentprevention and drop protection features.

FIG. 9B further illustrates protrusion 752 of actuation member 950 in aposition ready to pierce sealing layer 764 when actuation member 950(e.g., telescoping cap) is moved in a distal direction. Applicator 900is further illustrated as including the spring feature 954 configured toprovide the biased force loaded aspect of the actuation member 950 aspreviously described.

FIG. 9C is a cutaway view of applicator 900 of FIG. 9A in a deployedconfiguration. As shown, second layer 124 has been removed beforedeployment and actuation member 950 is shown as having been moved in thedistal direction and side flexure 956 depressed, causing protrusion 752to pierce sealing layer 764 and activate insertion assembly 118.

FIG. 10A illustrates another applicator 1000 for applying on-skinassembly 102 to skin of a host including a removable cap 1012 configuredas a sealing element, in accordance with some embodiments. FIG. 10B is apartially exploded view of applicator 1000 of FIG. 10A. Discussion ofapplicator 1000 will now take place with reference to both FIGS. 10A and10B. Applicator 1000 is substantially the same as applicator 700 ofFIGS. 7A and 7B, except as described below. Applicator 1000 comprises ahousing 1004, which may function substantially the same as housing 704.Applicator 1000 further comprises a telescoping cap 1050 that functionsas an actuation member. Applicator 1000 may not include second layer 124or frangible safety member 766 of FIGS. 7A and 7B. Instead, applicator1000 may include a removable cap 1012 configured to couple with a distalportion of telescoping cap 1050 actuation member via threads 1014. Insome embodiments, a layer 1052 permeable to a sterilizing gas, e.g.,Tyvek®, may be included under removable cap 1012 or alternativelyattached to removable cap 1012 such that layer 1052 is removed withremovable cap 1012. Threads 1014 disposed on removable cap 1012 may beconfigured to mate with threads (not shown) disposed on an insidesurface of the cap forming actuation member 1050. Removable cap 1012 maybe detached from actuation member 1050 by twisting removable cap 1012with respect to telescoping cap 1050, or vice versa. Since telescopingcap actuation member 1050 is thus coupled to removable cap 1012,applicator 1000 cannot be activated while removable cap 1012 is securedto applicator 1000. Accordingly, removable cap 1012 provides not only asealing element configured to provide a sterile barrier and a vaporbarrier between an internal and external environment of housing 1004,but also at least premature deployment prevention and drop protectionfeatures.

Embodiments Including a Flexible Shell

Some embodiments can include a flexible member configured as a shell orcover, which is disposed over the housing and operatively coupled to theactuation member. For example, FIG. 11A illustrates another applicator1100 for applying on-skin assembly 102 to skin of a host including aflexible member 1160 disposed over at least a portion of a housing 1104,in accordance with some embodiments. Although not shown, applicator 1100may further include insertion assembly 118 and on-skin assembly 102 asdescribed in connection with at least FIGS. 1A-1C. Applicator 1100comprises housing 1104, which may encapsulate insertion assembly 118 andon-skin assembly 102. Applicator 1100 may further comprise an actuationmember 1150 disposed on a side of housing 1104 and configured to, uponactivation, cause insertion assembly 118 to insert at least a portion ofon-skin assembly into the skin of a host. Applicator 1100 may furthercomprise flexible member 1160 disposed over housing 1104. Applicator1100 may further comprise second layer 124, which may seal a distalportion of flexible member 1160. Thus, second layer 124 in conjunctionwith flexible member 1160 provide a sealing element configured toprovide a sterile barrier and a vapor barrier between an internal andexternal environment of housing 1104. As shown in FIG. 11A, flexiblemember 1160 may comprise a flexible section 1162 configured to bedisposed over actuation member 1150 such that when flexible section 1162is pressed, actuation member 1150 is activated. In some embodiments,flexible section 1162 may be bistable in that it has two states: afirst, loaded state and a second, deployed state. In such embodiments,flexible section 1162 may provide a positive visual tamper indicationwhen in the second, deployed state. Moreover, the flexible nature offlexible member 1160 may additionally provide premature deploymentprevention and drop protection features by absorbing energy that mightotherwise provide a physical shock to applicator 1100.

FIG. 11B is a zoomed view of a portion of flexible member 1160 of FIG.11A disposed over actuation member 1150. FIG. 11B merely shows flexiblesection 1162 of flexible member 1160 in greater detail.

FIG. 12A illustrates another applicator 1200 for applying on-skinassembly 102 to skin of a host including a flexible member 1260 having abistable configuration that provides a visual indication of deployment,in accordance with some embodiments. FIG. 12B is a zoomed view of aportion of the bistable configuration of flexible member 1200 of FIG.12A. Applicator 1200 is substantially the same as applicator 1100 ofFIGS. 11A and 11B, except the actuation member (not shown) is disposedon a proximal portion of the housing (not shown) and flexible member1260 comprises a molded accordion-like section 1262 disposed on aproximal portion of flexible member 1260 and configured to be disposedover the actuation member such that when molded accordion-like section1262 is pressed, the top-mounted actuation member is activated. FIG. 12Aillustrates molded accordion-like section 1262 in the first, loadedstate, while FIG. 12B illustrates molded accordion-like section 1262 inthe second, deployed state.

FIG. 13A is an exploded view of another applicator 1300 for applyingon-skin assembly 102 to skin of a host including a flexible member 1360comprising a frangible member 1364 configured to cover an actuationmember 1350, in accordance with some embodiments. Applicator 1300 issubstantially the same as applicator 1100 of FIGS. 11A and 11B, exceptas described below. Applicator 1300 comprises housing 1104 of FIGS. 11Aand 11B, which comprises actuation member 1150 disposed on a side ofhousing 1104. Applicator 1300 further comprises a flexible member 1360,which itself comprises a frangible member 1364 and a frangible tab 1366.Applicator 1300 further comprises second layer 124 and, in someembodiments, first layer 122, disposed over a distal opening in flexiblemember 1360. In this way, flexible member 1360, second layer 124, and inembodiments including it, first layer 122, may form a sealing elementconfigured to provide a sterile barrier and a vapor barrier between andinternal environment and an external environment of housing 1304. Bypulling down on frangible tab 1366 and then pulling around applicator1300, frangible tab 1366 and frangible member 1360 may be removed inpreparation of using applicator 1300. Thus, at least frangible member1360 and frangible tab 1366 may simultaneously provide jointsterilization and moisture seals, tamper indication, as well aspremature deployment prevention and drop protection features.

FIG. 13B is a condensed view of applicator 1300 of FIG. 13A beforeremoval of frangible member 1360 and frangible tab 1366. FIG. 13Cillustrates applicator 1300 of FIG. 13A and 13B having the frangiblemember 1364 removed, thereby exposing actuation member 1350.

FIG. 14 illustrates another applicator 1400 for applying on-skinassembly 102 to skin of a host including a main portion 1460 disposedover at least a portion of applicator 1400 and comprising a flexiblematerial, in accordance with some embodiments. Applicator 1400 comprisesa housing 1404 configured to house insertion assembly 118 (not shown)and comprising an aperture 106 (not shown) through which on-skinassembly 102 (not shown) can pass. Applicator 1400 further comprises anactuation member 1470 configured to, upon activation, cause theinsertion assembly to insert at least the portion of on-skin assembly102 into the skin of the host. Main portion 1460 may comprise, forexample, rubber, silicone, or any other flexible, soft material thatprovides shock protection as well as grip to a user. Main portion 1460may be overmolded together with housing 1404. Main portion 1460 mayadditionally cover actuation member 1470, thereby providing some measureof accidental activation protection, as well as providing additionalsealing for applicator 1400. Main portion 1460 may extend over at leasta proximal portion of housing 1404, thereby providing both a grip forthe host as well as drop protection. Main portion 1460 may comprise anelastomeric material configured to absorb at least a portion of energyimparted to applicator 1400 when dropped. Furthermore, in otherembodiments, main portion 1464 may be removed by pulling a flexible tab1466 away from applicator 1400 to reveal a hidden button. In suchembodiments, main portion 1464 can provide additional tamper indicationor button activation prevention features.

Additional Embodiments

Alternatively or in addition to a removable cap, various embodiments caninclude one or more other features configured to provide a sterilizationseal and/or moisture barrier. A subset of such embodiments may comprisea single housing without a top or bottom cap. For example, FIG. 15Aillustrates a perspective view of an applicator 1500 for applyingon-skin assembly 102 to skin of a host including a peelable layer 1524configured to seal a distal opening 106 in a housing 1504 and to furtherseal an actuation member 1550, in accordance with some embodiments.Applicator 1500 comprises housing 1504 configured to house insertionassembly 118 and comprises aperture 106 through which on-skin assembly102 can pass. Applicator 1500 further comprises actuation member 1550disposed on a side of housing 1504 and configured to, upon activation,cause insertion assembly 118 to insert at least a portion of on-skinassembly into the skin of a host. In some embodiments, peelable layer1524 is coupled to at least a portion of housing 1524. For example, asshown in at least FIG. 15A peelable layer 1524 is configured to sealaperture 106 and actuation member 1550. Thus, peelable layer 1524 formsa sealing element configured to provide a sterile barrier and/or a vaporbarrier between an internal and external environment of housing 1504. Insome embodiments, peelable layer 1524 is a single piece forming thesealing element. Applicator 1500 may be readied for use by removingpeelable layer 1524, thereby exposing both aperture 106 and actuationmember 1550. In this way, peelable layer 1524 may also simultaneouslyprovide a tamper indication, premature deployment prevention and dropprotection features. FIG. 15B illustrates applicator 1500 of FIG. 15Ahaving peelable layer 1524 removed.

FIG. 16A illustrates another applicator 1600 for applying on-skinassembly 102 to skin of a host including a peelable layer 1624configured to seal a distal aperture 106 in a housing 1604, to furtherseal an actuation member 1650, and to further seal a vent 1662 permeableto a sterilizing gas, in accordance with some embodiments. FIG. 16B is apartially exploded view of applicator 1600 of FIG. 16A. Applicator 1600comprises a housing 1604 configured to house an insertion assembly, suchas insertion assembly 118 shown in FIG. 8B, and comprises an aperture106 through which an on-skin assembly, such as on-skin assembly 102shown in FIG. 1B, can pass. Applicator 1600 further comprises actuationmember 1650 disposed on a side of housing 1604 and configured to, uponactivation, cause insertion assembly 118 to insert at least a portion ofon-skin assembly into the skin of a host. Applicator 1600 furthercomprises vent 1662 configured to be permeable to a sterilizing gas. Insome embodiments, a porous polymeric component (e.g., a Porex® plug) maybe inserted into vent 1662. In some embodiments, vent 1662 may bedisposed on a side of housing 1604, for example, in some embodiments,facing substantially radially outward and substantially perpendicular toaperture 106. In some embodiments, peelable layer 1624 is coupled to atleast a portion of housing 1624. For example, as shown in at least FIG.16A peelable layer 1624 is configured to seal aperture 106, actuationmember 1650, and vent 1662, e.g., alone two faces of the applicator, oneof which comprises vent 1662. Thus, peelable layer 1624 forms a sealingelement configured to provide a sterile barrier and/or a vapor barrierbetween an internal and external environment of housing 1604. Forexample, peelable layer 1624 may be adhered to housing 1604 therebysealing aperture 106 on a distal face of housing 1604 but not yetsealing vent 1662. Applicator 1600 may then be subjected to asterilizing gas, which may permeate still-exposed vent 1662, therebysterilizing the inside of housing 1604. Peelable layer 1624 may then bedisposed over vent 1662 on a second face of housing 1604, therebysealing vent 1662 and providing a moisture barrier. Applicator 1600 maybe readied for use by removing peelable layer 1624, thereby exposingboth aperture 106 and actuation member 1650. In this way, peelable layer1624 may also simultaneously provide a tamper indication, prematuredeployment prevention and drop protection features.

FIG. 17A illustrates a perspective view of an applicator 1700 forapplying on-skin assembly 102 to skin of a host including a peelablelayer 1724 configured to seal a distal aperture 106 in a housing 1704and a inset plug or cap 1770 configured to seal an actuation member1750, in accordance with some embodiments. Applicator 1700 compriseshousing 1704 configured to house insertion assembly 118 and comprises anaperture 106 through which on-skin assembly 102 can pass. Applicator1700 further comprises actuation member 1750 (see FIGS. 17B and 17C)disposed on a side of housing 1704 and configured to, upon activation,cause insertion assembly 118 to insert at least a portion of on-skinassembly into the skin of a host. Applicator 1700 further comprisespeelable layer 1724 coupled to at least a portion of housing 1724. Forexample, as shown in at least FIG. 17A peelable layer 1724 is configuredto seal aperture 106. Applicator 1700 further comprises inset plug 1770configured to seal around actuation member 1750. Thus, peelable layer1724 and inset plug 1770 form a sealing element configured to provide asterile barrier and/or a vapor barrier between an internal and externalenvironment of housing 1704. As will be described in more detail inconnection with FIGS. 17B and 17C, applicator 1700 may be readied foruse by removing peelable layer 1724 and inset plug 1770, therebyexposing aperture 106 and actuation member 1750, respectively. In thisway, peelable layer 1724 and/or inset plug 1770 may simultaneouslyprovide at least tamper indication and premature deployment preventionfeatures.

FIG. 17B illustrates applicator 1700 of FIG. 17A with inset plug 1770removed. As shown, once inset plug 1770 is removed actuation member 1750is exposed and readied for activation.

FIG. 17C illustrates the applicator of FIG. 17B with peelable layer 1724further at least partially removed. As shown, once peelable layer 1724is removed aperture 106 is exposed and applicator 1700 is readied foruse by a host.

FIG. 36A illustrates a perspective view of an applicator 3600 includinga housing 3604, a sliding safety lock feature 3640, and an actuationmember 3650, in accordance with some embodiments. Safety lock feature3640 may include at least one button located near the top of housing3604. In some embodiments, safety lock feature 3640 includes two buttonslocated at opposite sides of the top of housing 3604. As shown in FIG.36A, actuation member 3650 is in a locked position in which an outersurface of actuation member 3650 may be flush with an outer surface 3606of housing 3604. In this locked position, actuation member 3650 cannotbe pressed by the user to trigger an internal insertion assembly. Asshown in FIG. 36B, safety lock feature 3640 has been pressed. Byactuating safety lock feature 3640, an internal latching componentreleases actuation member 3650 from the locked position to an unlockedposition. The outer surface of actuation member 3650 protrudes radiallyoutwards from the outer surface 3606 of housing 3604. In this unlockedposition, actuation member 3650 can be pressed by the user to trigger aninternal insertion assembly.

FIG. 37A illustrates a perspective view of an applicator 3700 includinga housing 3704 and a toggleable actuation member 3750, in accordancewith some embodiments. Toggleable actuation member 3750 may feature twostates: a locked state and an unlocked state. As shown in the figure,toggleable actuation member 3750 is in a locked state. In this state, anouter surface 3752 of toggleable actuation member 3750 protrudes at anangle from an outer surface 3706 of housing 3704. The angle oftoggleable actuation member 3750 can signify to the user that theapplicator is locked and cannot be triggered for sensor insertion.Further, toggleable actuation member 3750 cannot be pressed radiallyinwards to trigger an internal insertion assembly. As shown in FIG. 37B,toggleable actuation member 3750 is in an unlocked state. A user canpress on a top portion of toggleable actuation member 3750 to deflecttoggleable actuation member 3750 such that out surface 3752 is flushwith the outer surface 3706 of housing 3704. In this state, toggleableactuation member 3750 can be pressed radially inward to trigger theinternal insertion assembly.

FIG. 38A illustrates a perspective view of an applicator 3800 includinga housing 3804 having an outer surface 3806, an actuation member 3850,and a rotating safety lock feature 3810, in accordance with someembodiments. As shown in the figure, housing 3804 may include anaperture 3808. Aperture 3808 may be configured for actuation member 3850to extend through. In a locked state, as shown in the figure, actuationmember 3850 is a spring button contained with an interior of housing3804. In this state, applicator 3800 cannot be triggered to insert asensor via actuation member 3850. As shown in FIG. 38B, rotating safetylock feature 3810 can be rotated in a clockwise or counterclockwisedirection. As a user rotates safety lock feature 3810, actuation member3850 is rotated in a corresponding direction within housing 3804. Theuser can rotate safety lock feature 3810 until actuation member 3850reaches an unlocked state. In the unlocked state, due to the spring likenature of actuation member 3850, actuation member 3850 extends out ofaperture 3808 past outer surface 3806. In this state, actuation member3850 can be pressed radially inwards by a user to trigger an internalinsertion assembly.

FIG. 39 illustrates a perspective view of an applicator 3900 including ahousing 3904, an actuation member 3950, a removable cap 3910, and arelease button 3920, in accordance with some embodiments. Release button3920 may be pressed to release removable cap 3910. In such embodiments,release button 3920 may feature a delatching assembly to detachremovable cap 3910 from housing 3904. Release button 3920 may beincorporated into other removable cap applicator embodiments, such asbut not limited to FIGS. 2A-2B, 4A-4B, 5A-5B, 6A-6B, 10A-10B, 18A-18B,34A-34D, and 35A-35B.

FIG. 40 illustrates a perspective view of an applicator 4000 including ahousing 4004, a safety button 4040, and an actuation member 4050, inaccordance with some embodiments. As shown in the figure, safety button4040 may be located at the top of housing 4004. In such embodiments,safety button 4040 may be pressed in a distal direction to changeactuation member 4050 from a locked state to an unlocked state.Actuation of safety button 4040 may disengage internal trigger lockfeatures preventing actuation of actuation member 4050.

Additional Removable Cap Embodiments

FIG. 18A illustrates a perspective view of an applicator 1800 forapplying on-skin assembly 102 to skin of a host including a removablecap 1812 configured to seal an actuation member and a peelable layerconfigured to seal a distal opening in a housing, in accordance withsome embodiments. FIG. 18B is a partially exploded view of applicator1800 of FIG. 18A. Applicator 1800 comprises a housing 1804 configured tohouse insertion assembly 118 (not shown) and comprising aperture 106through which on-skin assembly 102 can pass. Applicator 1800 furthercomprises actuation member 1850 disposed on a proximal (i.e., top) ofhousing 1804 and configured to, upon activation, cause insertionassembly 118 to insert at least a portion of on-skin assembly into theskin of a host. In some embodiments actuation member 1850 protrudes fromthe proximal portion of housing 1804. Applicator 1800 may furthercomprises vent 1862 configured to be permeable to a sterilizing gas. Insome embodiments, a porous polymeric component (e.g., a Porex® plug) maybe inserted into vent 1862. In some embodiments, vent 1862 may bedisposed on a distal portion of housing 1804, for example, adjacent toaperture 106, and may face in substantially the same distal direction asaperture 106. Applicator 1800 further comprises peelable layer 1824coupled to at least a portion of housing 1804. For example, as shown inat least FIG. 18A peelable layer 1824 is configured to seal aperture 106and vent 1862 along a single planar surface (i.e., a distal surface ofhousing 1804). Thus, peelable layer 1824 forms a sealing elementconfigured to provide a sterile barrier and/or a vapor barrier betweenan internal and external environment of housing 1804.

Applicator 1800 further comprises removable cap 1812 configured tocouple with a proximal (i.e., top) portion of housing 1804. In someembodiments, removable cap 1812 further comprises one or more ridges orrecesses 1842 configured to provide a tactile indication of grip to thehost. In some embodiments, removable cap 1812 is configured to couplewith housing 1804 via threads. For example, threads 1814 disposed onremovable cap 1812 may be configured to mate with threads 1808 disposedon housing 1804. In some embodiments, applicator 1804 may furthercomprise a tamper-evident twist-off collar 1830, disposed at a matinglocation between housing 1804 and removable cap 1812. As previouslydescribed in connection with FIGS. 5A and 5B, a first portion 1830 a oftamper-evident twist-off collar 1830 may be coupled to removable cap1812 and a second portion 1830 b of tamper-evident twist-off collar 1830may be coupled to housing 1804. Removable cap 1812 may be detached fromhousing 1804 by twisting removable cap 1812 with respect to housing1804, or vice versa, until first portion 1830 a breaks free of secondportion 1830 b, and threads 1808 and 1814 are no longer mated and thenpulling removable cap 1812 and housing 1804 apart. In its integralstate, removable cap 1812 may provide a seal (e.g., a sterile barrierand a moisture or water vapor barrier) with housing 1804. In itsseparated state, tamper-evident twist-off collar 1830 may provide anindication of tampering to a user. Accordingly, peelable layer 1824,tamper-evident twist-off collar 1830, and removable cap 1812 may form asealing element.

FIG. 19A illustrates a perspective view of an applicator 1900 forapplying on-skin assembly 102 to skin of a host including a frangiblecap 1912 configured to seal an actuation member 1950 and a peelablelayer 1924 configured to seal a distal aperture 106 in a housing 1904,in accordance with some embodiments. FIG. 19B is a partially explodedview of applicator 1900 of FIG. 19A. Applicator 1900 may comprisesubstantially the same components as applicator 1800 of FIGS. 18A and18B, however, omitting tamper-evident twist-off collar 1830, threads1808 and 1814, and replacing removable cap 1812 with frangible cap 1912and pull tab 1966. For example, housing 1904, aperture 106, vent 1962,actuation member 1950 and peelable layer 1924 correspond with housing1804, aperture 106, vent 1862, actuation member 1850 and peelable layer1824, respectively. Furthermore, applicator 1900 may further include aprotrusion 1920 configured to inhibit applicator 1900 from rolling, aspreviously described in connection with FIG. 2.

Frangible cap 1912 is configured to couple with a proximal portion ofhousing 1904. In some embodiments, frangible cap 1912 comprises pull tab1966. Frangible cap 1912 is configured to be removed by pulling on pulltab 1966, thereby releasing frangible cap 1912. In this way, frangiblecap 1912, and peelable layer 1924 may form a sealing element configuredto provide a sterile barrier and/or a vapor barrier between an internalenvironment and an external environment of housing 1904. Frangible cap1912 further provides a tamper indicator for a host using applicator1900 such that if frangible cap 1912 is broken, tampering would bevisually evident to a user. Frangible cap 1912 additionally providespremature deployment prevention and drop protection features in that,until removed, it prevents access to actuation member 1950.

FIG. 34A illustrates a perspective view of an applicator 3400 forapplying on-skin assembly 102 to skin of a host including a removablecap 3410 configured to seal applicator 3400, in accordance with someembodiments. Applicator 3400 may include a housing 3404 having a mainportion 3408. Main portion 3408 may be overmolded with housing 3404. Insome embodiments, main portion 3408 is overmolded with actuation member3450. Further, main portion 3408 may be comprised of, for example,rubber, silicone, or any other flexible, soft material. Main portion3408 may provide shock protection as well as grip to a user.Additionally, main portion 3408 may comprise an elastomeric materialconfigured to absorb at least a portion of energy imparted to applicator3400 when dropped.

Applicator 3400 may include an actuation member 3450 (e.g. push button)that is formed integral with housing 3404. Actuation member 3450 may beconfigured to be pressed by a user to activate an internal insertionassembly 3470 (see FIG. 34B). In some embodiments, after removal ofremovable cap 3410, housing 3404 is configured to be pressed downagainst a surface (e.g. skin of a user) to unlock actuation member 3450.Housing 3404 may be actuated along an inner housing 3406 to alignactuation member 3450 with a trigger arm of insertion assembly 3470.Actuation member 3450 may then be pushed in a lateral direction toactuate trigger arm and activate insertion assembly 3470.

As shown in FIG. 34B, applicator, removable cap 3410 may be secured tohousing 3404 by interlocking cap threads 3414 and corresponding threads3416. Furthermore, a seal 3420 may be configured to be compressedbetween removable cap 3410 and a distal portion 3418 of housing 3404.Seal 3420 may be comprised of an elastomer and/or other compressiblematerials. Seal 3420 may be configured to provide a gas barrier and/orvapor barrier between applicator 3400 and the surrounding environment.Although not shown, removable cap 3410 may be detached from housing 3404by twisting removable cap 3410 with respect to housing 3404, or viceversa, until cap threads 3414 and corresponding threads 3416 of housing3404 are no longer mated with each other. Removable cap 3410 may includegrooves 3412 for improved grip by the user during attachment ordetachment of cap 3410 to housing 3404.

As shown in FIG. 34C, a bottom layer 3460 may be coupled to a distal endof removable cap 3410 and seal an aperture 3422 of removable cap 3410.Bottom layer 3460 may be similar to first layer 122 of FIG. 1A. Bottomlayer 3460 may be permeable to a sterilizing gas (e.g., ethylene oxide,or ETO). Moreover, bottom layer 3460 may comprise Tyvek® material,although any other material permeable to a sterilizing gas may beutilized. Bottom layer 3460 may allow for the ingress and egress of asterilizing gas through removable cap 3410 during manufacture. As shownin FIG. 34D, without bottom layer 3460, removable cap 3410 may includean open aperture 3422. Furthermore, removable cap 3410 may include atleast one aperture channel 3424. In some embodiments, removable cap 3410includes at least two aperture channels 3424. In some embodiments,removable cap 3410 includes at least three aperture channels 3424. Insome embodiments, removable cap 3410 includes at least four aperturechannels 3424. In some embodiments, removable cap 3410 includes at least6 aperture channels 3424. Each aperture channels 3424 may be configuredto allow for a sterilizing gas to ingress into housing 3404. In someembodiments, aperture channels 3424 are formed within a platform 3402.Platform 3402 may be a raised platform from the distal end of removablecap 3410. Platform 3402 may be configured to be spaced a certaindistance from an on-skin sensor assembly 102. Aperture channels 3424 maybe open slots spaced equidistantly along the circumference of platform3402.

As such, sterilizing gas from a surrounding environment of applicator3400 may ingress through bottom layer 3460, pass through aperturechannels 3424, and then ingress into the internal components ofapplicator 3400. An opposite process can occur for egress of thesterilizing gas from within applicator 3400, through aperture channels3424, through bottom layer 3460, and out into a surrounding environmentof applicator 3400.

FIG. 35A illustrates a perspective view of an applicator 3500 includinga removable cap 3510. Applicator 3500 may also include a housing 3504and an actuation member 3550. Removable cap 3510 may be removablyattached to housing 3504. As shown in FIG. 35B, housing 3504 includesinternal threads 3514 and removable cap 3510 includes external threads3516. In such embodiments, internal threads 3514 may be located in theinterior of housing 3504 and thus hidden or partially obscured from theuser after the user removes removable cap 3510 from housing 3504. Inother embodiments, housing 3504 may include exterior threads that arenot contained within the interior of housing 3504 and instead protrudefrom an exposed lower body of housing 3504. In such embodiments,removable cap 3510 may include corresponding internal threads that arehidden or partially obscured from the user. In some embodiments,removable cap 3510 may include at least one groove 3512 for improvedgrip by the user during attachment or detachment of cap 3510 to housing3504.

Embodiments Including Multiple Peelable Layers

Some embodiments can include one or more peelable layers (e.g., sheetsof material which are coupled (e.g. adhesively, heat staking) to aportion of the applicator and easily removable from the housing by apeeling action) which is coupled to, or integrally formed with, aremovable cap. FIG. 20A illustrates a perspective view of an applicator2000 for applying on-skin assembly 102 to skin of a host including afirst peelable layer 2024 configured to seal a distal aperture 106 in ahousing 2004 and a second peelable layer 2064 configured to seal anactuation member 2050 disposed in a proximal opening in the housing, inaccordance with some embodiments. FIG. 20B illustrates the actuationmember of the applicator of FIG. 20A in each of a pre-activated positionand an activated position. Applicator 2000 comprises a housing 2004configured to house insertion assembly 118 (not shown) and comprisingaperture 106 (not shown) through which on-skin assembly 102 can pass.Applicator 2000 further comprises actuation member 2050 disposed on aproximal (i.e., top) of housing 2004 and configured to, upon activation,cause insertion assembly 118 to insert at least a portion of on-skinassembly into the skin of a host. In some embodiments actuation member2050 is recessed into the proximal portion of housing 2004. Applicator200 further comprise first peelable layer 2024 is configured to sealaperture 106 in housing 2004 and second peelable layer 2064 configuredto seal actuation member 2050. Accordingly, first peelable layer 2024and second peelable layer 2064 may form a sealing element configured toprovide a sterile barrier and/or a vapor barrier between an internal andexternal environment of housing 2004. Applicator 2000 may be readied foruse by removing first peelable layer 2024 and second peelable layer2064. Accordingly, first peelable layer 2024 and second peelable layer2064 may simultaneously provide a tamper indication and prematuredeployment prevention feature.

FIG. 21A illustrates another applicator 2100 for applying on-skinassembly 102 to skin of a host including a inset plug 2170 configured toseal an actuation member 2150 and a peelable layer 2124 configured toseal a distal aperture 106 in a housing 2104, in accordance with someembodiments. Applicator 2100 comprises housing 2104 configured to houseinsertion assembly 118 and comprises an aperture 106 through whichon-skin assembly 102 can pass. Applicator 2100 further comprisesactuation member 2150 (see FIG. 21C) disposed on a proximal (i.e., top)portion of housing 2104 and configured to, upon activation, causeinsertion assembly 118 to insert at least a portion of on-skin assemblyinto the skin of a host. In some embodiments, actuation member 2150 isrecessed into the proximal portion of housing 2104. Applicator 2100further comprises peelable layer 2124 coupled to at least a portion ofhousing 2104. For example, peelable layer 2124 is configured to sealaperture 106 (see FIG. 21B). Applicator 2100 further comprises insetplug 2170 configured to seal actuation member 2150. Thus, peelable layer2124 and inset plug 2170 form a sealing element configured to provide asterile barrier and/or a vapor barrier between an internal and externalenvironment of housing 2104. Applicator 2100 may further comprise one ormore ridges or recesses 2144 configured to provide a tactile indicationof grip to the host. In some embodiments, applicator 2100 may furthercomprise comprises at least one protrusion 2120 configured to inhibitrolling of applicator 2100. Protrusion 2120 may also function as anorientation indicator for the user.

In an alternate embodiment, housing 2104 may be a deformable containercapable of flexing inwards and outwards. In such embodiments, asqueezing of housing 2104 may activate an insertion assembly withinhousing 2104, such as insertion assembly 118 (shown in FIG. 8B). Thedeformation caused by the squeezing of housing 2104 may decouple atrigger arm or latch (not shown) which can release the insertionassembly. Furthermore, in such embodiments, ridges or recesses 2144 maybe activation indicators to notify the user where to squeeze in order toactivate and fire the insertion assembly.

As shown more detail by FIGS. 21B and 21C, applicator 2100 may bereadied for use by removing peelable layer 2124 and inset cap 2170,thereby exposing aperture 106 and actuation member 2150, respectively.In this way, peelable layer 2124 and/or inset plug 2170 maysimultaneously provide at least tamper indication and prematuredeployment prevention features.

FIG. 21B illustrates applicator 2100 of FIG. 21A having peelable layer2124 removed. As shown, once peelable layer 2124 is removed aperture 106is exposed.

FIG. 21C illustrates applicator 2100 of FIG. 21A having inset cap 2170removed. As shown, once inset cap 2170 is removed actuation member 2150is exposed and readied for activation.

FIG. 22A illustrates a perspective view of an applicator 2200 forapplying on-skin assembly 102 to skin of a host including a firstpeelable layer 2224 configured to seal a distal aperture 106 in ahousing 2204 and to seal a vent 2262 (optional) permeable to asterilizing gas and a second peelable layer 2264 configured to seal anactuation member (not shown) disposed in a proximal opening in housing2204, in accordance with some embodiments. FIG. 22B is a partiallyexploded view of applicator 2200 of FIG. 22A. Applicator 2200 may besubstantially the same as applicator 2000 of FIGS. 20A and 20B, exceptas described below. Applicator 2200 comprises housing 2204, firstpeelable layer 2224, actuation member (not shown), and second peelablelayer 2264, which correspond to housing 2004, first peelable layer 2024,actuation member (not shown), and second peelable layer 2064 ofapplicator 2000, respectively. Applicator 2200 further comprises vent2262, which may correspond substantially to vent 1962 as previouslydescribed in connection with of FIGS. 19A and 19B. Accordingly, firstpeelable layer 1924 is configured to seal both aperture 106 of housing2204 and vent 2262. Of note, vent 2262 being disposed on a distalportion of housing 2204 adjacent to aperture 106 may additionallyprovide at least one protrusion 2220 configured to inhibit rolling ofapplicator 2200. Protrusion 2220 may also function as an orientationindicator for the user.

Embodiments Utilizing Protective Cups

FIG. 23 illustrates a collapsible cup 2390 having a removable lid 2392and configured to enclose an applicator 2300 for applying on-skinassembly 102 to skin of a host configured to fit within, in accordancewith some embodiments. Collapsible cup 2390 has a removable and/orpeelable lid 2392. Collapsible cup 2390 is configured to act as asealing element that seals applicator 2300 from an environment outsidecollapsible cup 2390. In some embodiments, collapsible cup 2390comprises an elastomer. In some embodiments, collapsible cup 2390 isconfigured to collapse after removal of removable and/or peelable lid2392. Applicator 2300 may correspond to any applicator, including anydescribed in this detailed description.

FIG. 24A illustrates a cup 2490 having a removable lid 2492 andconfigured to enclose an applicator 2400 for applying on-skin assembly102 to skin of a host, in accordance with some embodiments. In someembodiments, cup 2390 is in injection molded cup. Cup 2490 is configuredto act as a sealing element that seals applicator 2400 from anenvironment outside cup 2490. Applicator 2400 (see FIG. 24B) may bereadied for use by peeling removable lid 2492 from cup 2390 and removingapplicator 2400 therefrom. Applicator 2400 may be substituted with anypreviously described applicator.

FIG. 24B is a cutaway view of cup 2490 and applicator 2400 of FIG. 24A.As shown, within cup 2490 is disposed applicator 2400. In someembodiments, cup 2490 may further comprise an on-skin assembly alignmentfeature 2494. In some embodiments, on-skin alignment feature 2494 mayfurther comprise a needle protection feature in that, by restraining atleast lateral movement of the needle of insertion assembly 118, on-skinassembly alignment feature 2494 not only protects the needle from damageor outside contact, it also keeps on-skin assembly 102 in properalignment.

Actuation Member Alternatives

The present application sets forth a plurality of different applicatorembodiments. However, the present application is not limited solely tothe isolated embodiments, described. For example, any actuation memberof any describe embodiment may be replaced with any other actuationmember previously described, as desired. Any actuation member may beused to activate an insertion assembly, such as insertion assembly 118(not shown). For example, any applicator may alternatively comprise anactuation member disposed on a side of the housing (see FIGS. 1A-6B,11A, 11B, 13A-17C and 25), an actuation member disposed on a proximal(i.e., top) portion of the housing (see FIGS. 12A, 12B, and 18A-22B), anactuation member that is a cap in and of itself (see FIGS. 7A-10B), anactuation member that arms via depression and activates via pressing ofa flexure (see FIG. 9), a common push button, a bistable button (seeFIGS. 11A-12B), or any of the above example, however, further permeableto a sterilizing gas (see FIGS. 25A-25B). In some embodiments, anyapplicator may comprise a plurality of actuation members, in whichdepression of one or more of the plurality of actuation members mayactivate an insertion assembly. In some embodiments, depression of atleast two actuation members, simultaneously or in sequence, may berequired to activate an insertion assembly.

FIG. 25A is a cutaway view of an applicator 2500 for applying on-skinassembly 102 to skin of a host including an actuation member 2550 thatis permeable to a sterilizing gas, in accordance with some embodiments.FIG. 25B is a zoomed view of the actuation member of FIG. 25A.Applicator 2500 comprises an actuation member 2550, which itselfcomprises a material that is permeable to a sterilizing gas, forexample, Porex®. The structure of applicator 2500 is not of importancehere and, thus, applicator 2500 may correspond to any applicator,including any described herein. Thus, any applicator described hereinmay have its actuation member replaced with actuation member 2550, e.g.,replaced with an actuation member that is permeable to a sterilizinggas. In such embodiments, any vent may be omitted as the actuationmember may also function as the vent.

Bulk Manufacturing, Sterilizing, and/or Sealing of Applicators

As previously stated, it may be desirable to be able to manufacture,sterilize and/or seal applicators in bulk. This would not only reducethe per-unit cost of manufacture, it would potentially decrease the costto consumers of the applicators. Accordingly, below are described a fewembodiments that may allow for bulk manufacturing, sterilizing and/orsealing of multiple applicators simultaneously.

FIG. 26A is a cutaway view of a soluble moisture barrier 2624 having aplurality of perforations 2628 for an applicator 2600 for applyingon-skin assembly 102 to skin of a host, in accordance with someembodiments. For example, soluble moisture barrier 2624 having one ormore perforations 2628 may be utilized as a sealing element and may bedisposed over an opening 2626 in a removable cap 2612, for example, aspreviously described in connection with at least FIGS. 1A-1C and 3A-3C.The applicator 2600 may be subjected to a sterilizing gas, which mayingress and then egress through one or more perforations 2628, therebysterilizing the components within applicator 2600. Once sterilization iscomplete, soluble moisture barrier 2624 may be subjected to atemperature sufficient to at least partially dissolve or reflow moisturebarrier material 2624 which can seal perforations 2628, as shown in FIG.26B. Thus, in one state, soluble moisture barrier 2624 acts as a vent toallow for sterilization of applicator 2600, and in another state,soluble moisture barrier 2624 acts as a seal for applicator 2600.

FIG. 26B is a cutaway view of soluble moisture barrier 2624 of FIG. 26Aafter heating such that soluble moisture barrier 2624 has cooled downand solidified. Soluble moisture barrier 2624 is configured toredistribute itself in a form in which plurality of perforations 2628are closed and sealed. Because the operative transforming method isapplication of heat sufficient to melt soluble moisture barrier material2624, bulk sterilization and moisture sealing of a plurality ofapplicators may be achieved without direct contact with components.

FIG. 27A is a cutaway view of a moisture barrier 2724 including anelastomeric layer 2724 b and a perforated layer 2724 a, in accordancewith some embodiments. Moisture barrier 2724 may be utilized as asealing element and may be integral to a removable cap 2712, forexample, as previously described in connection with any previous figureillustrating a removable cap. Perforated layer 2724 a may be considereda first portion of a sealing element and may comprise a plurality ofperforations 2728 and an adhesive layer 2746 disposed on a first side ofperforated layer 2724 a. Elastomeric layer 2724 b may be considered asecond portion of the sealing element and may comprise a portionpermeable to a sterilizing gas. Elastomeric layer 2724 b is disposedadjacent to the first side of perforated layer 2724 a. Elastomeric layer2724 b is configurable in a first configuration where elastomeric layer2724 b is spatially separated from perforated layer 2724 a, providing apathway for a sterilizing pass to pass through the plurality ofperforations 2729 and the portion of elastomeric layer 2724 a permeableto the sterilizing gas. Elastomeric layer 2724 b may transition to asecond configuration where elastomeric layer 2724 b is adhered toperforated layer 2724 a via adhesive layer 2746, removing the pathwayfor the sterilizing gas and causing moisture barrier 2724 to beimpermeable to the sterilizing gas. In some other embodiments, adhesivelayer 2746 may not be included, and elastomeric layer 2724 b may bedrawn against perforated layer 2724 a without the need for adherence,thereby sealing the applicator. FIG. 27A illustrates the firstconfiguration.

As shown in FIG. 27A, applicator 2700 may be subjected to a sterilizinggas, which may ingress and then egress through plurality of perforations2728 in perforated layer 2724 a and through a transmissive layer 2730(e.g., Tyvek®) permeable to the sterilizing gas, thereby sterilizing thecomponents within applicator 2700. Once sterilization is complete,applicator 2700 may be subjected to a partial vacuum, thereby creating apressure gradient sufficient to transition elastomeric layer 2724 b fromthe first configuration to the second configuration. Due to the pressuregradient, elastomeric layer 2724 b is drawn against perforated layer2427 a which seals moisture barrier 2724 from sterilizing gas andmoisture, as shown in FIG. 27B. Generically, this concept covers anydesign that utilizes pressure gradient to actuate a valve that can beclosed after gaseous sterilization (e.g. Ethylene Oxide sterilization).For example, another embodiment may include an elastomeric stopper thatis configured to move to close air/vapor passage when a vacuum of asufficient flow rate is applied.

FIG. 27B is a cutaway view of moisture barrier 2724 of FIG. 27Aillustrating elastomeric layer 2724 b and perforated layer 2724 a in thesecond orientation such that the moisture barrier is impermeable to thesterilizing gas and to moisture, in accordance with some embodiments.Because the operative transforming method is the application of apartial vacuum sufficient to actuate elastomeric layer 2724 b from thefirst configuration to the second configuration, batch sterilizationand/or vapor (e.g. water vapor) sealing of a plurality of applicatorsmay be achieved simultaneously by subjecting a plurality of applicatorsto the partial vacuum simultaneously. This may aid in high efficiencysterilization of a plurality of applicators.

FIG. 28A illustrates a tray 2802 configured to hold a plurality ofapplicators 2800 for bulk sterilization and moisture barrier sealing, inaccordance with some embodiments. The plurality of applicators 2800 mayeach, for example, have a structure similar to that described inconnection with FIGS. 27A and 27B except wherein elastomeric layer 2724b is disposed on an outside of perforated layer 2724 a. In suchembodiments, elastomeric layer 2724 b would be in the firstconfiguration as previously described. The plurality of applicators 2800may be disposed on tray 2802.

As shown in FIG. 28A, applicators 2800 may be subjected to a sterilizinggas, which may ingress and then egress through plurality of perforations2728 in perforated layer 2724 a and through the transmissive layer 2730(e.g., Tyvek®, see FIGS. 27A-B) of elastomeric layer 2724 b permeable tothe sterilizing gas, thereby sterilizing the components within each ofthe plurality of applicators 2800. Once sterilization is complete, aforce applicator 2804 may be applied to the plurality of applicators2800 subjecting them to a force sufficient to transition elastomericlayer 2824 b in each of the plurality of applicators 2800 from the firstconfiguration to the second configuration, thereby rendering moisturebarrier 2824 impermeable to the sterilizing gas and to moisture. Such atransition is as shown in FIG. 28B.

FIG. 28B is a zoomed view of tray 2802 of FIG. 28A illustrating each ofthe plurality of applicators 2800 in the first configuration, permeableto a sterilizing gas, and the second configuration impermeable to thesterilizing gas and to moisture. Because the operative transformingmethod is application of a force sufficient to actuate each applicator'selastomeric layer 2724 b from the first configuration to the secondconfiguration, batch sterilization and/or vapor sealing of a pluralityof applicators may be achieved simultaneously by subjecting a pluralityof applicators to the physical force simultaneously via force applicator2804.

FIG. 29 is an exploded view of a sealing element comprising a firstlayer 2922 permeable to a sterilizing gas and a second layer 2924impermeable to the sterilizing gas and moisture, in accordance with someembodiments. The sealing element may be integral to a removable cap2912, for example, as previously described in connection with anyprevious figure illustrating a removable cap.

First layer 2922 may comprise Tyvek®, although any other materialpermeable to a sterilizing gas may be utilized. Application of firstlayer 2922 to removable cap 2912 may allow for the subsequent ingressand egress of a sterilizing gas during manufacture. Second layer 2924may comprise a metallic foil, although any other material impermeable tomoisture (e.g., water vapor) may be applied, for example, a metallicfoil (e.g. aluminum, titanium), a metallic substrate, aluminum oxidecoated polymer, parylene, a polymer coated with a metal applied viavapor metallization, silicon dioxide coated polymer, or any materialhaving a moisture vapor transmission rate less than 10 grams/100 in² orpreferably less than 1 grams/100 in². First layer 2922 and second layer2924 may seal an opening (not shown) in removable cap 2912. Applicationof second layer 2924 over first layer 2922 after sterilization mayfurther provide a moisture barrier for applicator 2900. Because secondlayer 2924 may be applied simultaneously to a plurality of applicators,batch sterilization and/or vapor sealing may be achieved.

FIG. 30A is a zoomed view of a sealing element comprising a vent 3062including a material permeable to a sterilizing gas, in accordance withsome embodiments. In some embodiments, the material may comprise aporous polymeric component such as Porex®, although any materialpermeable to a sterilizing gas may be utilized. The sealing element maybe integral to a removable cap 3012, for example, as previouslydescribed in connection with any previous figure illustrating aremovable cap. One or more applicators utilizing the sealing elementcomprising vent 3062 may be subjected to a sterilizing gas, which mayingress and egress the applicators via vent 3062. Once sterilization iscomplete, the sealing element comprising vent 3062 may be subjected to atemperature sufficient to form a sintered layer 3063 (see FIG. 30B) inthe porous polymeric component of vent 3062.

FIG. 30B is a zoomed view of the sealing element of FIG. 30Aillustrating sintered layer 3063 of vent 3062, which is impermeable tothe sterilizing gas. Because the operative transforming method isapplication of heat sufficient to sinter the porous polymeric componentof vent 3062, batch sterilization and/or vapor sealing of a plurality ofapplicators may be achieved simultaneously.

In an alternate embodiment, applicators may be enclosed in a containerafter sterilization is complete. The container may enclose theapplicator and function as a moisture barrier. This may aid in batchsterilization and/or vapor sealing of a plurality of applicators. Insome embodiments, the container may be a bag, a wrap, a thermoform, orsome form of kitted device.

Methods of Manufacturing

FIG. 32 is a flowchart 3200 illustrating a method of manufacturing anapplicator for applying on-skin assembly 102 to skin of a host, inaccordance with some embodiments. Steps in flowchart 3200 may beperformed for manufacturing any applicator as previously described inconnection with any of the previous figures. Although certain steps areset forth below, a method of manufacturing such an applicator maycomprise more, fewer, or different steps, in the same or different orderfrom that set forth below. Moreover, in some embodiments, this methodmay be utilized to manufacture a plurality of applicators in batches.

Flowchart 3200 comprises block 3202, which includes providing aninsertion assembly configured to insert at least a portion of theon-skin assembly into the skin of the host. For example, on-skinassembly 102 may be provided as previously described in connection withat least FIG. 1B.

Flowchart 3200 further comprises block 3204, which includes providing ahousing configured to receive the insertion assembly, the housingcomprising an aperture through which the on-skin assembly can pass. Sucha housing may be as previously described in connection with any of FIGS.1A-30.

Flowchart 3200 further comprises block 3206, which includes providing anactuation member configured to, upon activation, actuate the insertionassembly to insert at least the portion of the on-skin assembly into theskin of the host. For example, any actuation member as previouslydescribed in connection with any of FIGS. 1A-30 may be provided.

Flowchart 3200 further comprises block 3208, which includes providing asealing element configured to provide a sterile barrier and/or a vaporbarrier between an internal environment of the housing and an externalenvironment of the housing. For example, a sealing element as previouslydescribed in connection with any of FIGS. 1A-30 may be provided. Forexample, such a sealing element may not necessarily comprise a singleelement but instead may comprise any combination of removable caps, withor without threads, first or second layers, sealing layers, peelablesealing layers, frangible members or caps, flexible members, O-rings,bags, or other seals, as previously described in connection with anycombination from FIGS. 1A-30.

FIG. 33 is a flowchart illustrating another method of manufacturing anapplicator for applying on-skin assembly 102 to skin of a host, inaccordance with some embodiments. Steps in flowchart 3300 may beperformed for manufacturing any applicator as previously described inconnection with any of the previous FIGs. Although certain steps are setforth below, a method of manufacturing such an applicator may comprisemore, fewer, or different steps, in the same or different order fromthat set forth below. Moreover, in some embodiments, this method may beutilized to manufacture a plurality of applicators in batches.

Flowchart 3300 comprises block 3302, which includes providing aninsertion assembly configured to insert at least a portion of theon-skin assembly into the skin of the host. For example, on-skinassembly 102 may be provided as previously described in connection withat least FIG. 1B.

Flowchart 3300 further comprises block 3304, which includes providing ahousing configured to receive the insertion assembly, the housingcomprising an aperture through which the on-skin assembly can pass. Sucha housing may be as previously described in connection with any of FIGS.1A-30.

Flowchart 3300 further comprises block 3306, which includes providing anactuation member configured to, upon activation, actuate the insertionassembly to insert at least the portion of the on-skin assembly into theskin of the host. For example, any actuation member as previouslydescribed in connection with any of FIGS. 1A-30 may be provided.

Flowchart 3300 further comprises block 3308, which includes exposing atleast an internal environment of the housing to a sterilizing gas. Forexample, an internal environment of any housing as previously describedin connection with FIGS. 1A-30 may be exposed to a sterilizing gas, suchas ethylene oxide (ETO), as previously described or by exposing anapplicator to the sterilizing gas before formation, provision,manufacture or application of a sealing element that transforms thehousing from permeable to the sterilizing gas to impermeable to at leastthe sterilizing gas.

Flowchart 3300 further comprises block 3310, which includes allowing foregress of the sterilizing gas from the internal environment of thehousing. For example, upon exposing the applicator to the sterilizinggas, the sterilizing gas may be removed and a sufficient amount of timemay elapse before continuing the manufacturing process to allow foregress of substantially all sterilizing gas from the internalenvironment of the housing.

Flowchart 3300 further comprises block 3312, which includes sealing theinternal environment of the housing from an external environment of thehousing. For example, a sealing element as previously described inconnection with any of FIGS. 1A-30 may be provided. For example, such asealing element may not necessarily comprise a single element butinstead may comprise any combination of removable caps, with or withoutthreads, first or second layers, sealing layers, peelable sealinglayers, frangible members or caps, flexible members, O-rings, bags, orother seals, as previously described in connection with any combinationfrom FIGS. 1A-30.

In some embodiments, at least sealing the internal environment of thehousing from an external environment of the housing is performedsimultaneously for a plurality of applicators. In some embodiments,sealing the internal environment of the housing from an externalenvironment of the housing comprises subjecting the plurality ofapplicators to a partial vacuum exceeding a threshold such that asealing element of each of the plurality of applicators transitions frombeing permeable to the sterilizing gas to being impermeable to thesterilizing gas, as previously described in connection with at leastFIGS. 27A and 27B.

In some other embodiments, sealing the internal environment of thehousing from an external environment of the housing comprises subjectingthe plurality of applicators to a physical force sufficient to cause asealing element of each of the plurality of applicators to transitionfrom a first physical configuration permeable to the sterilizing gas toa second physical configuration impermeable to the sterilizing gas, aspreviously described in connection with FIGS. 28A and 28B.

In yet other embodiments, sealing the internal environment of thehousing from an external environment of the housing comprises subjectinga sealing element, comprising a plurality of perforations, of each theplurality of applicators to a temperature sufficient to at leastpartially melt each of the sealing elements thereby sealing theplurality of perforations in each of the sealing elements, as previouslydescribed in connection with FIGS. 26A and 26B.

In yet other embodiments, sealing the internal environment of thehousing from an external environment of the housing comprises subjectinga sealing element, comprising a porous polymeric component, of each ofthe plurality of applicators to a temperature sufficient to form asintered layer in the porous polymeric component of each sealingelement, as previously described in connection with FIGS. 30A and 30B.

In yet other embodiments, sealing the internal environment of thehousing from an external environment of the housing comprises depositinga layer impermeable to the sterilizing gas on at least a portion of eachof the plurality of applicators, as previously described in connectionwith FIG. 29. In some such embodiments, the layer comprises at least oneof a metallic foil (e.g. aluminum, titanium), a metallic substrate,aluminum oxide coated polymer, parylene, a polymer coated with a metalapplied via vapor metallization, silicon dioxide coated polymer, or anymaterial having a moisture vapor transmission rate less than 10grams/100 in² or preferably less than 1 grams/100 in².

The specification and figures of U.S. patent application Ser. No.15/387,088, filed on Dec. 21, 2016 and published as U.S. Publication No.2017/0188910 A1, are hereby incorporated by reference herein in theirentirety, and form a part of this application.

It should be appreciated that all methods and processes disclosed hereinmay be used in any glucose monitoring system, continuous orintermittent. It should further be appreciated that the implementationand/or execution of all methods and processes may be performed by anysuitable devices or systems, whether local or remote. Further, anycombination of devices or systems may be used to implement the presentmethods and processes.

The above description presents the best mode contemplated for carryingout the present invention, and of the manner and process of making andusing it, in such full, clear, concise, and exact terms as to enable anyperson skilled in the art to which it pertains to make and use thisinvention. This invention is, however, susceptible to modifications andalternate constructions from that discussed above that are fullyequivalent. Consequently, this invention is not limited to theparticular embodiments disclosed. On the contrary, this invention coversall modifications and alternate constructions coming within the spiritand scope of the invention as generally expressed by the followingclaims, which particularly point out and distinctly claim the subjectmatter of the invention. While the disclosure has been illustrated anddescribed in detail in the drawings and foregoing description, suchillustration and description are to be considered illustrative orexemplary and not restrictive.

All references cited herein are incorporated herein by reference intheir entirety. To the extent publications and patents or patentapplications incorporated by reference contradict the disclosurecontained in the specification, the specification is intended tosupersede and/or take precedence over any such contradictory material.

Unless otherwise defined, all terms (including technical and scientificterms) are to be given their ordinary and customary meaning to a personof ordinary skill in the art, and are not to be limited to a special orcustomized meaning unless expressly so defined herein. It should benoted that the use of particular terminology when describing certainfeatures or aspects of the disclosure should not be taken to imply thatthe terminology is being re-defined herein to be restricted to includeany specific characteristics of the features or aspects of thedisclosure with which that terminology is associated. Terms and phrasesused in this application, and variations thereof, especially in theappended claims, unless otherwise expressly stated, should be construedas open ended as opposed to limiting. As examples of the foregoing, theterm ‘including’ should be read to mean ‘including, without limitation,’‘including but not limited to,’ or the like; the term ‘comprising’ asused herein is synonymous with ‘including,’ ‘containing,’ or‘characterized by,’ and is inclusive or open-ended and does not excludeadditional, unrecited elements or method steps; the term ‘having’ shouldbe interpreted as ‘having at least;’ the term ‘includes’ should beinterpreted as ‘includes but is not limited to;’ the term ‘example’ isused to provide exemplary instances of the item in discussion, not anexhaustive or limiting list thereof; adjectives such as ‘known’,‘normal’, ‘standard’, and terms of similar meaning should not beconstrued as limiting the item described to a given time period or to anitem available as of a given time, but instead should be read toencompass known, normal, or standard technologies that may be availableor known now or at any time in the future; and use of terms like‘preferably,’ ‘preferred,’ ‘desired,’ or ‘desirable,’ and words ofsimilar meaning should not be understood as implying that certainfeatures are critical, essential, or even important to the structure orfunction of the invention, but instead as merely intended to highlightalternative or additional features that may or may not be utilized in aparticular embodiment of the invention. Likewise, a group of itemslinked with the conjunction ‘and’ should not be read as requiring thateach and every one of those items be present in the grouping, but rathershould be read as ‘and/or’ unless expressly stated otherwise. Similarly,a group of items linked with the conjunction ‘or’ should not be read asrequiring mutual exclusivity among that group, but rather should be readas ‘and/or’ unless expressly stated otherwise.

Where a range of values is provided, it is understood that the upper andlower limit, and each intervening value between the upper and lowerlimit of the range is encompassed within the embodiments.

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations may be expressly set forth herein for sakeof clarity. The indefinite article ‘a’ or ‘an’ does not exclude aplurality. A single processor or other unit may fulfill the functions ofseveral items recited in the claims. The mere fact that certain measuresare recited in mutually different dependent claims does not indicatethat a combination of these measures cannot be used to advantage. Anyreference signs in the claims should not be construed as limiting thescope.

It will be further understood by those within the art that if a specificnumber of an introduced claim recitation is intended, such an intentwill be explicitly recited in the claim, and in the absence of suchrecitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases ‘at least one’ and ‘one or more’ to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles ‘a’ or ‘an’ limits any particular claim containing suchintroduced claim recitation to embodiments containing only one suchrecitation, even when the same claim includes the introductory phrases‘one or more’ or ‘at least one’ and indefinite articles such as ‘a’ or‘an’ (e.g., ‘a’ and/or ‘an’ should typically be interpreted to mean ‘atleast one’ or ‘one or more’); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, those skilled in the art will recognize that such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of ‘two recitations,’ without othermodifiers, typically means at least two recitations, or two or morerecitations). Furthermore, in those instances where a conventionanalogous to ‘at least one of A, B, and C, etc.’ is used, in generalsuch a construction is intended in the sense one having skill in the artwould understand the convention (e.g., ‘a system having at least one ofA, B, and C’ would include but not be limited to systems that have Aalone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). In those instances where aconvention analogous to ‘at least one of A, B, or C, etc.’ is used, ingeneral such a construction is intended in the sense one having skill inthe art would understand the convention (e.g., ‘a system having at leastone of A, B, or C’ would include but not be limited to systems that haveA alone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). It will be furtherunderstood by those within the art that virtually any disjunctive wordand/or phrase presenting two or more alternative terms, whether in thedescription, claims, or drawings, should be understood to contemplatethe possibilities of including one of the terms, either of the terms, orboth terms. For example, the phrase ‘A or B’ will be understood toinclude the possibilities of ‘A’ or ‘B’ or ‘A and B.’

All numbers expressing quantities of ingredients, reaction conditions,and so forth used in the specification are to be understood as beingmodified in all instances by the term ‘about.’ Accordingly, unlessindicated to the contrary, the numerical parameters set forth herein areapproximations that may vary depending upon the desired propertiessought to be obtained. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of anyclaims in any application claiming priority to the present application,each numerical parameter should be construed in light of the number ofsignificant digits and ordinary rounding approaches.

Furthermore, although the foregoing has been described in some detail byway of illustrations and examples for purposes of clarity andunderstanding, it is apparent to those skilled in the art that certainchanges and modifications may be practiced. Therefore, the descriptionand examples should not be construed as limiting the scope of theinvention to the specific embodiments and examples described herein, butrather to also cover all modification and alternatives coming with thetrue scope and spirit of the invention.

What is claimed is:
 1. A method of manufacturing an applicatorconfigured to apply an on-skin assembly to skin of a host, the methodcomprising: providing an insertion assembly including a needleconfigured to insert at least a portion of the on-skin assembly into theskin of the host; providing a housing configured to receive theinsertion assembly, the housing comprising an aperture through which theon-skin assembly is configured to pass; exposing at least an internalenvironment of the housing to a sterilizing gas; allowing for egress ofthe sterilizing gas from the internal environment of the housing; andsealing the internal environment of the housing from an externalenvironment of the housing, wherein the sealing comprises subjecting theapplicator to a partial vacuum exceeding a threshold such that a sealingelement of the applicator transitions from being permeable to thesterilizing gas to being impermeable to the sterilizing gas.
 2. Themethod of claim 1, wherein at least sealing the internal environment ofthe housing from an external environment of the housing is performedsimultaneously for a plurality of applicators.
 3. The method of claim 2,wherein sealing the internal environment of the housing from an externalenvironment of the housing comprises subjecting the plurality ofapplicators to a physical force sufficient to cause a sealing element ofeach of the plurality of applicators to transition from a first physicalconfiguration permeable to the sterilizing gas to a second physicalconfiguration impermeable to the sterilizing gas.
 4. The method of claim2, wherein sealing the internal environment of the housing from anexternal environment of the housing comprises subjecting a sealingelement, comprising a plurality of perforations, of each the pluralityof applicators to a temperature sufficient to at least partially melteach of the sealing elements thereby sealing the plurality ofperforations in each of the sealing elements.
 5. The method of claim 2,wherein sealing the internal environment of the housing from an externalenvironment of the housing comprises subjecting a sealing element,comprising a porous polymeric component, of each of the plurality ofapplicators to a temperature sufficient to form a sintered layer in theporous polymeric component of each sealing element.
 6. The method ofclaim 2, wherein sealing the internal environment of the housing from anexternal environment of the housing comprises depositing a layerimpermeable to the sterilizing gas on at least a portion of each of theplurality of applicators.
 7. The method of claim 6, wherein the sealingelement comprises at least one of a metallic foil, a metallic substrate,an aluminum oxide coated polymer, parylene, a polymer coated with ametal applied via vapor metallization, a silicon dioxide coated polymer,or any material having a moisture vapor transmission rate less than 10grams/100in2 or preferably less than 1 grams/100in2.
 8. A method ofmanufacturing an applicator configured to apply an on-skin assembly toskin of a host, the method comprising: providing an insertion assemblyincluding a needle configured to insert at least a portion of theon-skin assembly into the skin of the host; providing a housingconfigured to receive the insertion assembly, the housing comprising anaperture through which the on-skin assembly is configured to pass;providing a sealing element configured to provide a sterile barrier anda vapor barrier between an internal environment of the housing and anexternal environment of the housing; and sealing the internalenvironment of the housing from the external environment of the housing,wherein the sealing comprises subjecting the applicator to a partialvacuum exceeding a threshold such that the sealing element of theapplicator transitions from being permeable to a sterilizing gas tobeing impermeable to the sterilizing gas.
 9. The method of claim 8,wherein the housing comprises a vent configured to be permeable to thesterilizing gas.
 10. The method of claim 9, wherein the sealing elementis configured to seal the vent.
 11. The method of claim 8, wherein thesealing element comprises a peelable layer coupled to at least a portionof the housing.
 12. The method of claim 11, wherein the peelable layeris configured to provide a tamper indication when removed.
 13. Themethod of claim 11, wherein the peelable layer is configured to seal adistal opening of the housing.
 14. The method of claim 11, wherein thepeelable layer is configured to seal a vent configured to be permeableto the sterilizing gas.